Suppressor of cytokine signaling 1 is required for the differentiation of CD4+ T cells

2005 ◽  
Vol 6 (7) ◽  
pp. 715-721 ◽  
Author(s):  
Ian M Catlett ◽  
Stephen M Hedrick
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling

Abstract 129: Suppressor of Cytokine Signaling 1 in Dendritic Cells Inhibits Myocardial Inflammation in Experimental Autoimmune Myocarditis

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Kazuko Tajiri ◽  
Kyoko Imanaka-Yoshida ◽  
Michiaki Hiroe ◽  
Nobutake Shimojo ◽  
Satoshi Sakai ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cytokine Signaling ◽  
Autoimmune Myocarditis ◽  
Dc Function ◽  
Autoreactive T Cell ◽  
Experimental Autoimmune Myocarditis ◽  
Experimental Autoimmune

Introduction: Autoimmunity is considered to play an important role in the development of myocarditis and dilated cardiomyopathy. Recent reports have indicated that a subgroup of myocarditis patients may benefit from immune-targeted therapies. Suppressor of cytokine signaling1 (SOCS1) is an intracellular, cytokine-inducible protein that regulates the responses of immune cells to cytokines. We therefore hypothesized that overexpression of SOCS1 may inhibit the inflammation of myocarditis and cardiomyopathy. Methods and Results: Myocarditis was induced by subcutaneous immunization with cardiac specific peptides derived from α-myosin heavy chain in BALB/c mice on days 0 and 7. Plasmid DNA encoding SOCS1 (pSOCS1) was injected intraperitoneally into mice on days 0, 5 and 10. pSOCS1 treatment significantly decreased heart-to-body weight ratios and the number of infiltrating cells in the heart. Echocardiography showed preserved contractile function in pSOCS1-treated mice. Although autoimmune myocarditis is a CD4+ T cell-mediated disease, pSOCS1 treatment does not have a direct suppressive effect on autoreactive T-cell activation. The introduced pSOCS1 suppressed proinflammatory cytokine production and STAT1 phosphorylation in dendritic cells (DCs). In addition, the proliferative responses of autoreactive CD4+ T cells co-cultured with DCs from pSOCS1-treated mice were much weaker than those of cells cultured with DCs from control plasmid-injected mice. These results suggested that the inoculated pSOCS1 may have been transfected into DCs and impaired DC function in vivo. Conclusion: The administration of pSOCS1 protected mice from the development of experimental autoimmune myocarditis, which was mediated by the inhibition of DC function that in turn reduced the activation of autoreactive CD4+ T cells.

scholarly journals Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice

2009 ◽  
Vol 133 (3) ◽  
pp. 437-446 ◽  
Author(s):  
Soichiro Fushimi ◽  
Tetsuya Ogino ◽  
Junko Hara ◽  
Tomohiro Takahata ◽  
Hiroshi Wakabayashi ◽  
...  
Keyword(s):  
T Cells ◽  
Concanavalin A ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling

scholarly journals HDAC3 restrains CD8-lineage genes to maintain a bi-potential state in CD4+CD8+ thymocytes for CD4-lineage commitment

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Rachael Laura Philips ◽  
Jeong-Heon Lee ◽  
Krutika Gaonkar ◽  
Pritha Chanana ◽  
Ji Young Chung ◽  
...  
Keyword(s):  
T Cells ◽  
Mhc Class Ii ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Lineage Commitment ◽  
Cytokine Signaling ◽  
Rna Seq ◽  
Kinetics Analysis ◽  
Tcr Signaling ◽  
Histone Deacetylase 3

CD4 and CD8 T cells are vital components of the immune system. We found that histone deacetylase 3 (HDAC3) is critical for the development of CD4 T cells, as HDAC3-deficient DP thymocytes generate only CD8SP thymocytes in mice. In the absence of HDAC3, MHC Class II-restricted OT-II thymocytes are redirected to the CD8 cytotoxic lineage, which occurs with accelerated kinetics. Analysis of histone acetylation and RNA-seq reveals that HDAC3-deficient DP thymocytes are biased towards the CD8 lineage prior to positive selection. Commitment to the CD4 or CD8 lineage is determined by whether persistent TCR signaling or cytokine signaling predominates, respectively. Despite elevated IL-21R/γc/STAT5 signaling in HDAC3-deficient DP thymocytes, blocking IL-21R does not restore CD4 lineage commitment. Instead, HDAC3 binds directly to CD8-lineage promoting genes. Thus, HDAC3 is required to restrain CD8-lineage genes in DP thymocytes for the generation of CD4 T cells.

scholarly journals A Role of Suppressor of Cytokine Signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated Interleukin 2 Production

2003 ◽  
Vol 197 (4) ◽  
pp. 425-436 ◽  
Author(s):  
Akira Matsumoto ◽  
Yoh-ichi Seki ◽  
Ryosuke Watanabe ◽  
Katsuhiko Hayashi ◽  
James A. Johnston ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Interleukin 2 ◽  
Sh2 Domain ◽  
Janus Kinase ◽  
Expression Level ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Cd28 Costimulation

Suppressor of cytokine signaling (SOCS)3 has been characterized as a negative feedback regulator in cytokine-mediated Janus kinase signal transducer and activator of transcription signaling. However, this study shows that T cells from transgenic mice expressing SOCS3 exhibit a significant reduction in interleukin (IL)-2 production induced by T cell receptor cross-linking when T cells are costimulated with CD28. Decreased protein expression in SOCS3+/− mice enhanced CD28-mediated IL-2 production, clearly indicating the correlation between expression level of SOCS3 and IL-2 production ability. The SOCS3 protein interacted with phosphorylated CD28 through its SH2 domain but not the kinase inhibitory region. In addition, a point mutation in the SOCS3 SH2 domain attenuated the inhibition of CD28 function in IL-2 promoter activation. Committed T helper (Th)2 cells exclusively expressed SOCS3 and production of Th2 cytokines, such as IL-4 and IL-5, was much less dependent on CD28 costimulation compared with interferon γ and IL-2 production in Th1 cells. Consistent with this notion, the expression level of SOCS3 in early T cell activation influenced the ability of IL-2 production induced by CD28 costimulation. Therefore, the SOCS3 may play an alternative role in prohibiting excessive progression of CD28-mediated IL-2 production.

scholarly journals Suppressor of Cytokine Signaling-1 Regulates Signaling in Response to Interleukin-2 and Other γc-dependent Cytokines in Peripheral T Cells

2003 ◽  
Vol 278 (25) ◽  
pp. 22755-22761 ◽  
Author(s):  
Ann L. Cornish ◽  
Mark M. Chong ◽  
Gayle M. Davey ◽  
Rima Darwiche ◽  
Nicos A. Nicola ◽  
...  
Keyword(s):  
T Cells ◽  
Interleukin 2 ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Peripheral T Cells

scholarly journals Cytokine-Induced Src Homology 2 Protein (Cis) Promotes T Cell Receptor–Mediated Proliferation and Prolongs Survival of Activated T Cells

2000 ◽  
Vol 191 (6) ◽  
pp. 985-994 ◽  
Author(s):  
Suling Li ◽  
Shangwu Chen ◽  
Xiufeng Xu ◽  
Anette Sundstedt ◽  
Kajsa M. Paulsson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Cell Receptor ◽  
Cytokine Signaling ◽  
Src Homology 2 ◽  
Src Homology

Members of the suppressor of cytokine signaling (SOCS) family were discovered as negative regulators of cytokine signaling by inhibition of the Janus kinase–signal transducer and activator of transcription (Jak-STAT) pathway. Among them, cytokine-induced Src homology 2 (SH2) protein (CIS) was found to inhibit the interleukin 3– and erythropietin-mediated STAT5 signaling pathway. However, involvement of SOCS proteins in other signaling pathways is still unknown. This study shows that the expression of CIS is selectively induced in T cells after T cell receptor (TCR) stimulation. In transgenic mice, with selective expression of CIS in CD4 T cells, elevated CIS strongly promotes TCR-mediated proliferation and cytokine production in vitro, and superantigen-induced T cell activation in vivo. Forced expression of CIS also prolongs survival of CD4 T cells after TCR activation. Molecular events immediately downstream from the TCR are not changed in CIS-expressing CD4 T cells, but activation of mitogen-activated protein (MAP) kinase pathways by TCR stimulation is significantly enhanced. Together with the increased MAP kinase activation, a direct interaction of CIS and protein kinase Cθ was also demonstrated. These results suggest that CIS is one of the important regulators of TCR-mediated T cell activation. The functions of CIS, enhancing TCR signaling and inhibiting cytokine signaling, may be important in the regulation of immune response and homeostasis.

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