Journal of Immunology and Clinical Research

microRNA Functions Intracellular Calcium Homeostasis in Naïve CD8+ T Cells

Review Article | Open Access

  • 1. Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Republic of Korea
  • 2. Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Republic of Korea
+ Show More - Show Less
Corresponding Authors
Tae-Don Kim, Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Yuseong-gu, Daejeon, Republic of Korea

Functional capability of effector CD8+ T cells on pathogen-infected cells to kill them requires the activation of naive CD8+ T cells by triggering the stimulation of T cell receptors (TCR) and costimulatory molecules. The proper activation of effector CD8+ T cells depends on the co-stimulation of both TCR and co-stimulatory molecules. Without co-stimulation effector CD8+ T cells are unable to produce activation-inducing genes such as IL-2 and proliferate upon with specific antigen. This condition refers as the anergy formation of effector CD8+ T cells. Activation and anergy formation of effector CD8+ T cells depend on the intracellular Ca2+ signaling, as it regulates the responsiveness of CD8+ T cells. This contribution of Ca2+ signaling has been well studied in effector CD8+ T cells with possible molecular mechanisms. But, the specific molecular mechanisms of Ca2+ signaling in naive CD8+ T cells related to anergy formation have not yet been well discussed, other than our previous study which reported about the contribution of miR-150 to regulate Ca2+ signaling in naive CD8+ T cells thereby regulating the responsiveness. Therefore, in this review we have summarized the already known role of Ca2+ signaling in naive and CD8+ T cells. Specially, we have highlighted the role of miR-150 in the regulation of naive CD8+ T cells’ responsiveness.


Chandimali N, Tae-Don K (2020) microRNA Functions Intracellular Calcium Homeostasis in Naïve CD8+ T Cells. J Immunol Clin Res 6(1): 1049.


•    Anergy
•    Immune tolerance
•    miR-150
•    Naïve
•    Hypo responsiveness


CRAC: Calcium Release-Activated Ca2+ Channel; PMCA: Plasma Membrane Ca2+ ATPase; TCR: T Cell Receptor; STIM1: Stromal-Interacting Molecule 1; TMEM20: Transmembrane Protein 20; NFAT: Nuclear factor of activated T-cells; AP-1: Activator Protein 1; ORAI1: CRAC Channel Protein 1


Unresponsiveness of the immune system to various tissues or substances which have the ability to elicit an immune response can be termed as the immune tolerance [1]. Depending on the state where it origin, immune tolerance can be classified into central tolerance and peripheral tolerance [2,3]. Central tolerance prefers the educating immune system to discriminate self and non-self and originates in thymus and bone marrow. Whereas the peripheral tolerance, which functions to prevent the over reactivity in immune system, originates in lymph nodes or other tissues [2]. Generally, the direct induction of this peripheral lymphocyte tolerance may cause the lack of response to foreign organisms via mal-functioned defense mechanisms, which is termed as anergy [4,5]. In the state of anergy, the immune system is unable to elicit immune responses against a specific antigen. Therefore, the phenotype of lymphocytes which fail to respond to specific antigens is called as the Anergic phenotype [6,7].

Anergy induction and its underlying molecular mechanisms have been well studied in effector T cells as a type of lymphocyte which plays a major role in immune response [5,7,8]. Among T cells, the cytotoxic T cells (CD8+ T cells) kill the infected or damaged cells [9]. It is essential to stimulate T cell receptors (TCR) together with its co-stimulatory molecules to trigger a balanced CD8+ T cell activation [6,10]. Mainly, both CD8+ T cell activation and anergy formation depend on the Calcium (Ca2+ ) - mediated signaling pathway. Ca2+ signaling pathway uses Ca2+ ions to drive various cellular processes mainly as signal transduction [11]. Even though, Ca2+ -mediated signaling in effector CD8+ T cell has been studied well, the molecular mechanism in naive T cells has not yet been studied much in the literature. Naive CD8+ T cells are CD8+ T cells which are not yet encountered its cognate antigen [12]. But, we have showed how Ca2+ signaling functions on naive CD8+ T cells, especially in the mean of activation and anergy formation in one of our previous studies. According to that paper, Ca2+ signaling in naive CD8+ T cells can be regulated by highly expressed microRNA (miR-150), small non-coding RNA which is having 22 nucleotides [13]. MicroRNAs are small endogenous RNAs, which is having 19-25 nucleotides [14]. Some of other previous studies also have showed that microRNAs regulate the immune tolerance or anergy in T cells including CD8+ T cells [15-17].

Considering the above mentioned findings related to immune tolerance and anergy formation, especially in CD8+ T cells, we have concluded the Ca2+ -mediated regulation in the responsiveness of effector CD8+ T cells. We also highlighted those regulations in naive CD8+ T cells. Finally, we have summarized the contribution of miR150 in the activation of naive CD8+ T cells and the regulation of CD8+ T cell responsiveness to prevent hypo or unresponsiveness.

Ca2+ mediated signaling regulates responsiveness of CD8+ T cells

Ca2+- mediated activation of Effector CD8+ T cell: Naive CD8+ T cells go through activation process after it encounters an appropriate antigen while migrating through secondary lymphoid organs. These activated Effector CD8+ T cells are functionally capable to mediate effector immune responses [18,19]. Those appropriate antigens with major histocompatibility complex stimulate TCR in this activation process of effector CD8+ T cells. For a proper activation, effector CD8+ T cells also require parallel stimulation of co-stimulatory receptors such as CD28 [13]. Mechanistically, stimulation of TCR increases the intracellular concentration of Ca2+ . This results the induced nuclear translocalization of Nuclear factor of activated T-cells (NFAT), a family of transcription factors which is important in immune response (20). Parallel, the co-stimulation of CD28 activates Activator protein 1 (AP-1) through the activation of PI3K signaling pathway. Interactions of NFAT with AP-1 in a transcriptional complex can increase the expression of CD8+ T cell activation related genes. Therefore, the co-stimulation of both NFAT and AP-1 is essential for the proper activation of effector CD 8+ T cells to be functionally capable [20,21].

Moreover, calcium release-activated Ca2+ (CRAC) channel and plasma membrane Ca2+ ATPase (PMCA) are important in the regulation of intracellular Ca2+ concentration during CD8+ T cell activation [22]. Upon TCR stimulation, the Ca2+ release from Endoplasm Reticulum (ER) with the help of inositol triphosphate receptor is induced. It results the elevated level of intracellular Ca2+ in cytoplasm. The higher concentration of intracellular Ca2+ associates with calmodulin, a multifunctional intermediate calcium-binding messenger protein, to activate PMCA there by exporting the Ca2+ from cell. On the other hand, Stromal-interacting molecule 1 (STIM1) regulates the balance of intracellular Ca2+ concentration in a cell by controlling the influx of Ca2+ [23]. For this function, STIM1 forms a complex with transmembrane protein 20 (TMEM20) which enable STIM1 binding to PMCA [24]. STIM1 can interact with CRAC channel protein 1 (ORAI1) there by opening CRAC channels to allow Ca2+ influx into cells [23]. Furthermore, it inhibits PMCA-mediated Ca2+ extrusion from cells [25]. Therefore, the complex of STIM1 and TMEM20 is contributed to keep the balance of Ca2+ concentration and activation of effector CD8+ T cell state. Therefore, CRAC, PMCA, STIM1 and TMEM20 play their essential roles in effector CD8+ T cell activation to make them functionally capable, without inducing anergeric phenotypes. Specially, TMEM20 plays an important role in effector CD8+ T cell activation by controlling STIM1 [13].

Even though, the specific role of TMEM20 has been studied well in effector CD8+ T cell during its activation, it has been not focused that much on naive CD8+ T cells.

Anergy formation in effector CD8+ T cell: Anergy, the unresponsiveness of immune cells considers as an important mechanism in the maintaining of peripheral immune tolerance [5]. T cell anergy inactivates the lymphocytes functionally following the appropriate antigen encounter. But, those cells with anergic phenotype remain alive for a long period under hypo responsiveness state as they are having a different life span from normal T cells [26]. Both CD4+ and effector CD8+ T cell anergy can be divided into two broad categories as clonal anergy and adaptive or in vivo anergy. Among them, clonal anergy is responsible for the growth arrest state while adaptive anergy tolerance is representing the inhibition of effector and proliferative functions of T cells [27].

Clonal anergy in CD4+ T cells can be induced by the stimulation of strong T cell receptor (TCR) signal when the co stimulation is absent [28]. According to previous studies, conditions which can induce new protein synthesis but is not complete enough to activate of CD 4+ T cells initiate and maintain the anergic state in CD4+ T cells [27]. Similarly to CD4+ T cells, effector CD8+ T cells also appeared to be anti-proliferative when it is in the state of clonal anergy [29]. Other than that, Mescher and colleagues have described another form of clonal anergy in effector CD8+ T cells named activation-induced non-responsiveness (AINR) [29]. Therefore, the proper co-stimulation is required to induce the activation over anergy formation in effector CD8+ T cells, which were stimulated by TCR, cannot produce Interleukin 2 (IL-2) if the co-simulation of molecules such as CD28 is absent. Also, they cannot proliferate upon subsequent stimulation by antigens. In this case, NFAT homodimerizes complexes itself and induces anergy in effector CD8+ T lymphocytes instead of working as a transcriptional factor [20,21,30].

Generally, the appropriate antigen should be present to T lymphocyte by an antigen presenting cell (APC) to begin productive response of effector CD8+ T lymphocytes. These APC present the antigen on its MHC II complex which activates costimulatory receptors in CD8+ T cell. However, when T cells interact with an antigen not presented by the APCs which is not specific, the effector CD8+ T cell undergoes anergy. It has also been shown that, even though, those antigens presented by APCs properly, induce the effector CD8+ T cell activation only weakly. This weak stimuli still activates NFAT sufficiently, but AP-1 is not, thereby the anergistic response takes place even with the costimulation [21]. Strong stimulation of T-cells either by IL-2 or by TCR/costimulatory receptors can break the anergy formation [10,31].

Therefore, the Ca2+ signaling in effector CD8+ T cells has critical role in the T cell activation and anergy formation (Figure 1). Although controlling intracellular Ca2+ levels in naïve CD8+ T cells is also critical for T cell activation, regulatory molecules and associated mechanisms that determine the Ca2+ signaling in naïve CD8+ T cell activation and anergy formation are largely unknown.

Contribution of miR-150 in naive CD8+ T cell to immune activation and tolerance via TMEM20-mediated Ca2+ signaling

Naive CD8+ T cells migrating within secondary lymphoid organs such as spleen and lymph nodes, can get activated upon stimulation by appropriate antigen [9]. Mostly, these cognate antigens are presented by dendritic cells. Upon activation, antigen?specific CD8+ T cells undergo clonal expansion and become effector CD8+ T cells [32,33]. Even though, it is not yet understood well, Ca2+ signaling plays a pivotal role in this activation of naïve CD8+ T cells and the responsiveness [13]. As a possible molecular mechanism of regulating Ca2+ signaling in naïve CD8+ T cells, we have reported a mechanism mediated by miR-150 in our previous study [13]. Generally the level of miR-150 is higher in naïve CD8+ T cells and reduces with TCR stimulation [34]. According to the above mentioned study, we showed how miR-150 controls the level of intracellular Ca2+ level in naïve CD8+ T cells through downregulating TMEM20. MiR-150, microRNA with 22 nucleotides, acts as an essential regulator in the activation of naïve CD8+ T cells by preventing hypo responsiveness and the expression of anergy-inducing genes upon TCR stimulation [13].

That study has shown that, the deficiency of miR-150 can induce the expression of anergy-inducing genes in naïve CD8+ T cells by using miR-150 -/- naïve CD8+ T cells. Mechanistically, the reduction of miR-150 in naïve CD8+ T cells induces TMEM20 expression [13]. Usually TMEM 20 co-localizes with STIM1 by making a complex to function in CD8+ T cells [24]. But, in naïve T cells, TMEM20 not localizes with STIM1 and act in STIM1- independent manner. Therefore, as this study suggest, various un-identified factors which can support TMEM20 function may induce TMEM20 in miR-150 reduce conditions. Elevated TMEM20 then inactivate PMCA activities, extrusion of intracellular Ca2+ from cells, in naïve CD8+ T cells [13]. Therefore, miR-150 induces the translocation of TMEM20 into PMCA by inactivating its functions.

However, there are many other intracellular Ca2+ regulators in CD8+ T cells including Calcium release-activated channels (CRAC), sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), sodium-calcium exchanger (NCX) and mitochondrial calcium uniporter (MCU) [35,36]. But in our previous study, we have proved that these regulators are not functioning in naïve CD8+ T cells as similar as in CD8+ effector T cells. Among those regulators, CRAC can reduce the uptake of Ca2+ but not the overall intracellular Ca2+ level. Therefore, the overall role of CRAC is limited in naïve CD8+ T cells compared to CD8+ effector T cells. Similarly, SERCA and NCX also are in inactivated conditions because those regulators are activated upon TCR stimulation [13]. When consider MCU, functions associate with mitochondria relocation [37]. Therefore, it is inactivated in naïve CD8+ T cells as it has un-polarized mitochondria at Ca2+ influx site. Thus, the function of MCU as Ca2+ regulator is different from CD8+ T cells which mitochondria relocate in immunological synapse.

Induced intracellular Ca2+ level in naïve CD8+ T cells by induced TMEM20 in miR-150 reduced conditions causes the elevation of NFAT activities thereby increase the expression of anergy-inducing genes such as Egr2, cbl-b and p27. Therefore, the reduction of miR-150 in naïve CD8+ T cells results induced expression of anergy-inducing genes (Figure 2) [13].



The responsiveness, activation and anergy formation, of effector and naive CD8+ T cells is regulated by the ca2+ signaling. Both cells have differences in the underlying molecular mechanisms of this regulation. To date, the mechanisms in effector CD8+ T cells have been well-studied. But, it is remaining to study more in naive CD8+ T cells. According to a paper published by our group previously, in miR-150 reduced conditions of naïve CD8+ T cells induce the anergy formation by inducing anergyinducing gene expression via TMEM20-mediated overexpression of intracellular Ca2+ concentration. In basal level, the miR-150 level is higher in naive CD8+ T cells than effector CD8+ T cells.

Activation or anergy formation is regulating by PMCA as main Ca2+ regulator in naïve CD8+ T cells. Whereas, other Ca2+ regulators also contribute to the Ca2+ regulation in effector CD8+ T cells to regulate the responsiveness of effector CD8+ T cells. Therefore, the anergy formation of naïve CD8+ T cells depend on the TMEM20 and it can be affected by miR-150 expression. As naïve CD8+ T cells are having higher level of miR-150, it may help it to maintain reproductive states in naive CD8+ T cells other than anergy state.


This work was supported by “R&D Convergence Program” of National Research Council of Science and Technology (CAP-18- 02-KRIBB).


1. Romagnani S. Immunological tolerance and autoimmunity. Intern Emerg Med. 2006; 1: 187-196.

2. Waldmann H. Mechanisms of immunological tolerance. Clin Biochem. 2016; 49: 324-328. 3. Pekkarinen PT. [Immunological tolerance]. Duodecim. 2015; 131: 628-635.

4. Kalekar LA, DL Mueller. Relationship between CD4 Regulatory T Cells and Anergy In Vivo. J Immunol. 2017; 198: 2527-2533.

5. Srinivasan M, KA Frauwirth. Reciprocal NFAT1 and NFAT2 Nuclear Localization in CD8+ Anergic T Cells Is Regulated by Suboptimal Calcium Signaling. J Immunol. 2007; 179: 3734-3741.

6. Yu-Xue Zhang, Yang-Yang Zhao, Jizhou Shen, Xun Sun, Yi Liu , Hang Liu, et al. Nanoenabled Modulation of Acidic Tumor Microenvironment Reverses Anergy of Infiltrating T Cells and Potentiates Anti-PD-1 Therapy. Nano Letters. 2019; 19: 2774-2783.

7. Yuka Maeda, Hiroyoshi Nishikawa, Daisuke Sugiyama, Danbee Ha, Masahide Hamaguchi, Takuro Saito, et al. Detection of Self-Reactive CD8? T Cells With an Anergic Phenotype in Healthy Individuals. Science. 2014; 346: 1536-1540.

8. Yuka Maeda, Hiroyoshi Nishikawa, Daisuke Sugiyama, Danbee Ha, Masahide Hamaguchi, Takuro Saito, et al. Detection of self-reactive CD8(+) T cells with an anergic phenotype in healthy individuals. Science. 2014; 346: 1536-1540.

9. Gerritsen B, A Pandit. The memory of a killer T cell: models of CD8+ T cell differentiation. Immunol Cell Biol. 2016; 94: 236-241.

10. Fernando Macián, Francisco García-Cózar, Sin-Hyeog Im, Heidi F Horton, Michael C Byrne, Anjana Rao. Transcriptional mechanisms underlying lymphocyte tolerance. Cell. 2002; 109: 719-731.s

11. Nowycky MC, AP Thomas. Intracellular calcium signaling. Journal of Cell Science. 2002; 115: 3715.

12. Gerritsen B, A Pandit. The memory of a killer T cell: models of CD8(+) T cell differentiation. Immunol Cell Biol. 2016; 94: 236-241.

13. Tae-Don Kim, Hong-Ryul Jung, Sang-Hwan Seo, Se-Chan Oh, Youngho Ban, Xiaoxia Tan, et al. MicroRNA-150 modulates intracellular Ca2+levels in naïve CD8+ T cells by targeting TMEM20. Sci Rep. 2017; 7: 2623.

14. Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol. 2018; 141: 1202-1207.

15. Nelomi Anandagoda, Joanna Cd Willis, Arnulf Hertweck, Luke B Roberts, Ian Jackson, M Refik Gökmen, et al. microRNA-142–mediated repression of phosphodiesterase 3B critically regulates peripheral immune tolerance. J Clin Invest. 2019; 129: 1257-1271.

16. Matthias Merkenschlager, Antoine Marcais. microRNAs calibrate T cell responses by regulating mTOR. Oncotarget. 2015; 6: 34059-34060.

17. Qiong Lou, Ruixian Liu, Xiangling Yang, Weiqian Li, Lanlan Huang, Lili Wei, et al. miR-448 targets IDO1 and regulates CD8(+) T cell response in human colon cancer. J Immunother Cancer 2019; 7: 210.

18. Croft M. Activation of naive, memory and effector T cells. Curr Opin Immunol. 1994; 6: 431-437.

19. Punt J. Chapter 4 - Adaptive Immunity: T Cells and Cytokines. In Cancer Immunotherapy (Second Edition). GC Prendergast, and EM Jaffee, eds. Academic Press, San Diego. 2013; 41-53.

20. Kuklina EM. Molecular mechanisms of T-cell anergy. Biochemistry (Mosc). 2013; 78: 144-156.

21. Noemi Soto-Nieves, Irene Puga, Brian T Abe, Sanmay Bandyopadhyay, Ian Baine, Anjana Rao, et al. Transcriptional complexes formed by NFAT dimers regulate the induction of T cell tolerance. J Exp Med. 2009; 206: 867-876.

22. Kelley M Fracchia, Christine Y Pai, Craig M Walsh. Modulation of T Cell Metabolism and Function through Calcium Signaling. Front Immunol. 2013; 4: 324.

23. Chan Young Park, Paul J Hoover, Franklin M Mullins, Priti Bachhawat, Elizabeth D Covington, Stefan Raunser, et al. STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. Cell. 2009; 136: 876-890.

24. Grigory Krapivinsky, Luba Krapivinsky, Stephanie C Stotz, Yunona Manasian, David E Clapham. POST, partner of stromal interaction molecule 1 (STIM1), targets STIM1 to multiple transporters. Proc Natl Acad Sci U S A. 2011; 108: 19234-19239.

25. Michael F Ritchie, Elsie Samakai, Jonathan Soboloff. STIM1 is required for attenuation of PMCA-mediated Ca2+ clearance during T-cell activation. EMBO J. 2012; 31: 1123-1133.

26. R Lechler, J G Chai, F Marelli-Berg, G Lombardi. The contributions of T-cell anergy to peripheral T-cell tolerance. Immunology. 2001; 103: 262-269.

27. Schwartz RH. Cell Anergy. Annual Review of Immunology. 2003; 21: 305-334.

28. S Mirshahidi, C T Huang, S Sadegh-Nasseri. Anergy in peripheral memory CD4(+) T cells induced by low avidity engagement of T cell receptor. J Exp Med. 2001; 194: 719-731.

29. M J Deeths, R M Kedl, M F Mescher. CD8+ T cells become nonresponsive (anergic) following activation in the presence of costimulation. J Immunol. 1999; 163: 102-110.

30. Schwartz RH. T cell anergy. Annu Rev Immunol. 2003; 21: 305-334.

31. Alexander Y Rudensky, Marc Gavin, Ye Zheng. FOXP3 and NFAT: partners in tolerance. Cell 2006; 126: 253-256.

32. Nu Zhang, Michael J Bevan. CD8+ T Cells: Foot Soldiers of the Immune System. Immunity. 2011; 35: 161-168.

33. Carmen Gerlach, Jan C Rohr, Leïla Perié, Nienke van Rooij, Jeroen W J van Heijst, Arno Velds, et al. Heterogeneous Differentiation Patterns of Individual CD8+ T Cells. Science. 2013; 340: 635.

34. Haoquan Wu, Joel R Neilson, Priti Kumar, Monika Manocha, Premlata Shankar, Phillip A Sharp, et al. miRNA profiling of naive, effector and memory CD8 T cells. PLoS One. 2007; 2: e1020.

35. Feske S. Calcium signalling in lymphocyte activation and disease. Nat Rev Immunol. 2007; 7: 690-702.

36. Balasubramanyam M, C Rohowsky-Kochan, JP Reeves, JP Gardner. Na+/Ca2+ exchange-mediated calcium entry in human lymphocytes. J Clin Invest. 1994; 94: 2002-2008.

37. Ariel Quintana, Christian Schwindling, Anna S Wenning, Ute Becherer, Jens Rettig, Eva C Schwarz, et al. T cell activation requires mitochondrial translocation to the immunological synapse. Proc Natl Acad Sci U S A. 2007; 104: 14418-14423.

Received : 06 May 2020
Accepted : 17 Jun 2020
Published : 18 Jun 2020
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
TEST Journal of Dentistry
ISSN : 1234-5678
Launched : 2014
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X