Constitutively CD40-activated B cells regulate CD8 T cell inflammatory response by IL-10 induction.
Constitutively CD40-activated B cells regulate CD8 T cell inflammatory response by IL-10 induction.
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DOI：
10.4049/jimmunol.1203364
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发表时间：
2013-04-01
期刊：
影响因子：
--
通讯作者：
Shimoda M
中科院分区：
文献类型：
--
作者：
Koni PA;Bolduc A;Takezaki M;Ametani Y;Huang L;Lee JR;Nutt SL;Kamanaka M;Flavell RA;Mellor AL;Tsubata T;Shimoda M
慢性炎症性疾病中B细胞暴露于高水平的CD40配体(CD40L、CD154)。此外，在自身免疫性疾病和淋巴瘤等人类疾病中也发现了同时表达CD40和CD40L的B细胞。然而，炎症状态下CD40激活的B细胞如何影响T细胞反应仍不清楚。在B细胞表达CD40配体转基因(CD40LTg)并接受自分泌CD40/CD40L信号的小鼠模型中，我们发现CD40LTg B细胞刺激记忆样CD4和CD8T细胞表达IL-10。CD8T细胞的这种IL-10表达依赖于干扰素-I和程序性细胞死亡蛋白1，对CD8T细胞的过度激活起关键作用。此外，在RAG-1−/−小鼠中过继转移幼稚的CD8T细胞通常会诱导与IL-17和干扰素γ细胞因子产生相关的结肠炎。利用这一模型，我们发现过继共转移CD40LTg B细胞，而不是野生型B细胞，显著降低了CD8T细胞中IL-17的应答，并调节了与IL-10诱导相关的结肠炎。因此，表达CD40L的B细胞可作为IL-10诱导炎性CD8 T细胞应答的治疗目标。一百九十四
B cells are exposed to high levels of CD40 ligand (CD40L, CD154) in chronic inflammatory diseases. In addition, B cells expressing both CD40 and CD40L have been identified in human diseases such as autoimmune diseases and lymphoma. However, how such constitutively CD40-activated B cells under inflammation may impact on T cell response remains unknown. Using a mouse model in which B cells express a CD40 ligand transgene (CD40LTg) and receive autocrine CD40/CD40L signaling, we show that CD40LTg B cells stimulated memory-like CD4 and CD8 T cells to express IL-10. This IL-10 expression by CD8 T cells was dependent on IFN-I and Programmed cell death protein 1, and was critical for CD8 T cells to counter-regulate their over activation. Furthermore, adoptive transfer of naïve CD8 T cells in RAG-1−/− mice normally induces colitis in association with IL-17 and IFNγ cytokine production. Using this model, we show that adoptive co-transfer of CD40LTg B cells, but not wild type B cells, significantly reduced IL-17 response and regulated colitis in association with IL-10 induction in CD8 T cells. Thus, B cells expressing CD40L can be a therapeutic goal to regulate inflammatory CD8 T cell response by IL-10 induction. 194
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影响因子：
4.4
作者：
CHEN, JZ;TROUNSTINE, M;HUSZAR, D
通讯作者：
HUSZAR, D
DOI：
10.4049/jimmunol.0803052
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Blair PA;Chavez-Rueda KA;Evans JG;Shlomchik MJ;Eddaoudi A;Isenberg DA;Ehrenstein MR;Mauri C
通讯作者：
Mauri C
DOI：
10.1084/jem.20092253
发表时间：
2010-06-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Feng T;Wang L;Schoeb TR;Elson CO;Cong Y
通讯作者：
Cong Y
影响因子：
32.4
作者：
Kamanaka, Masahito;Kim, Sean T.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
4.4
作者：
Koschella, M;Voehringer, D;Pircher, H
通讯作者：
Pircher, H