Absence of signaling into CD4⁺ cells via C3aR and C5aR enables autoinductive TGF-β1 signaling and induction of Foxp3⁺ regulatory T cells.
Absence of signaling into CD4⁺ cells via C3aR and C5aR enables autoinductive TGF-β1 signaling and induction of Foxp3⁺ regulatory T cells.
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作者：
C3a and C5a receptor (C3aR and C5aR) signaling by dendritic cells and CD4+ cells provides costimulatory and survival signals to T effector cells. Here, we demonstrate that when C3aR and C5aR signals are not transduced into CD4+ cells, PI-3Kγ-AKT-mTOR signaling ceases, PKA activation increases, auto-inductive transforming growth factor- β1 (TGF-β1) signaling initiates, and CD4+ cells become Foxp3+ T regulatory cells (iTregs). Endogenous TGF-β1 suppresses C3aR and C5aR signaling by preventing C3a and C5a production and upregulating C5L2, an alternate C5a receptor. Absent C3aR and C5aR signaling decreases costimulatory molecule and interleukin-6 production and augments interleukin-10 production. The resulting iTregs exert robust suppression, possess enhanced stability, and suppress ongoing autoimmune disease. Human iTregs with potent suppressor activity can be induced exploiting this insight.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.4049/jimmunol.0900691
发表时间：
2009-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
O'Gorman WE;Dooms H;Thorne SH;Kuswanto WF;Simonds EF;Krutzik PO;Nolan GP;Abbas AK
通讯作者：
Abbas AK
影响因子：
32.4
作者：
Haribhai D;Williams JB;Jia S;Nickerson D;Schmitt EG;Edwards B;Ziegelbauer J;Yassai M;Li SH;Relland LM;Wise PM;Chen A;Zheng YQ;Simpson PM;Gorski J;Salzman NH;Hessner MJ;Chatila TA;Williams CB
通讯作者：
Williams CB
影响因子：
4.4
作者：
Liu, Jinbo;Lin, Feng;Medof, M. Edward
通讯作者：
Medof, M. Edward
影响因子：
4.8
作者：
Cain, SA;Monk, PN
通讯作者：
Monk, PN