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STAT3 Regulates Proliferation and Survival of CD8+ T Cells : Enhances Effector Responses to HSV-1 Infection, and Inhibits IL-10+ Regulatory CD8+ T Cells in Autoimmune Uveitis
Joint Authors
Lee, Yong-Jun
Egwuagu, Charles E.
Dambuza, Ivy M.
Yu, Cheng-Rong
Frank, Gregory M.
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-09-24
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
STAT3 regulates CD4+ T cell survival and differentiation.
However, its effects on CD8+ T cells are not well understood.
Here, we show that in comparison to WT CD8+ T cells, STAT3-deficient CD8+ T cells exhibit a preactivated memory-like phenotype, produce more IL-2, proliferate faster, and are more sensitive to activation-induced cell death (AICD).
The enhanced proliferation and sensitivity to AICD correlated with downregulation of class-O forkhead transcription factors (FoxO1, FoxO3A), p21waf1, p27KIP1, Bcl-2, OX-40, and upregulation of FasL, Bax, and Bad.
We examined whether STAT3-deficient CD8+ T cells can mount effective response during herpes simplex virus (HSV-1) infection and experimental autoimmune uveitis (EAU).
Compared to WT mice, HSV-1-infected STAT3-deficient mice (STAT3KO) produced less IFN-γ and virus-specific KLRG-1+ CD8+ T cells.
STAT3KO mice are also resistant to EAU and produced less IL-17-producing Tc17 cells.
Resistance of STAT3KO to EAU correlated with marked expansion of IL-10-producing regulatory CD8+ T cells (CD8-Treg) implicated in recovery from autoimmune encephalomyelitis.
Thus, increases of IL-6-induced STAT3 activation observed during inflammation may inhibit expansion of CD8-Tregs, thereby impeding recovery from uveitis.
These results suggest that STAT3 is a potential therapeutic target for upregulating CD8+ T cell-mediated responses to viruses and suggest the successful therapeutic targeting of STAT3 as treatment for uveitis, derived, in part, from promoting CD8-Treg expansion.
American Psychological Association (APA)
Yu, Cheng-Rong& Dambuza, Ivy M.& Lee, Yong-Jun& Frank, Gregory M.& Egwuagu, Charles E.. 2013. STAT3 Regulates Proliferation and Survival of CD8+ T Cells : Enhances Effector Responses to HSV-1 Infection, and Inhibits IL-10+ Regulatory CD8+ T Cells in Autoimmune Uveitis. Mediators of Inflammation،Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-465744
Modern Language Association (MLA)
Yu, Cheng-Rong…[et al.]. STAT3 Regulates Proliferation and Survival of CD8+ T Cells : Enhances Effector Responses to HSV-1 Infection, and Inhibits IL-10+ Regulatory CD8+ T Cells in Autoimmune Uveitis. Mediators of Inflammation No. 2013 (2013), pp.1-10.
https://search.emarefa.net/detail/BIM-465744
American Medical Association (AMA)
Yu, Cheng-Rong& Dambuza, Ivy M.& Lee, Yong-Jun& Frank, Gregory M.& Egwuagu, Charles E.. STAT3 Regulates Proliferation and Survival of CD8+ T Cells : Enhances Effector Responses to HSV-1 Infection, and Inhibits IL-10+ Regulatory CD8+ T Cells in Autoimmune Uveitis. Mediators of Inflammation. 2013. Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-465744
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-465744