CD4+ regulatory T cell control TH17 responses in a Stat3-dependent manner (Science, 2009, 326:986-991)

報告日期: 2010/04/13
報告時間: 17:10/18:00
報告學生: 楊秀菊
講評老師: 楊倍昌
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990413-3.pdf

CD4+ regulatory T cells control TH17 responses in a STAT3-dependent manner

Ashutosh Chaudhry, Dipayan Rudra, Piper Treuting, Robert M. Samstein, Yuqiong Liang, Arnold Kas, Alexander Y. Rudensky

Science, 2009, 326:986-991

 

Speaker: 楊秀菊

Commentator: Dr. 楊倍昌

Date: 13 Apr, 2010    17:10~18:00

Place: Room 602

 

Abstract:

CD4+ regulatory T cells (Treg cells, CD4+ Foxp3+ T cells) play an important role to keep the delicate balance of Th1, Th2 and Th17 responses in inflammation.  Cytokine secretion by Treg cells influence effector T cell lineages in the microenvironment. Different “classes” of Treg cells have been found in lymphoid and nonlymphoid tissues and mediate tissue-specific immunoregulatory functions. Previously, the authors found that the T-bet and IRF4 (interferon regulatory factor 4) expression of Treg cells is essential for Th1 and Th2 responses, respectively.  In this paper, the authors demonstrated that Treg cells require STAT3 signaling to control Th17 response.  By using STAT3 conditional knock-out mouse system under the control of Foxp3 promoter, they found that Treg cells with intact STAT3 was required for the suppression of fatal colitis.  After adoptive transfer of STAT3 -/- Treg cells along with CD4+ Foxp3- T cells into the Rag2-/- receipt mice, the inflammation at the mucosa (cecum, skin and salivary gland) of mice received of STAT3-/- Treg is more severe than that of mice received wild type STAT3 Treg cells. To gain a clear mechanism of STAT3–dependent action of Treg cells, they compared the gene expression pattern of STAT3 -/- and STAT wt Treg cells isolated from Stat3fl/fl and Stat3fl/wt mice but they did not get any significance.  Together, their findings suggest that the STAT3-mediated functions allow Treg to adapt to a particular environment and to control appropriate “class”-specific immune-mediated inflammation.

 

References

1.    Koch A. M. et al., The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nature Immunology, 2009, 10: 595-602

2.    Zheng Y., et al., Regulatory T cell suppressor program co-opts transcription factor IRF4 to control Th2 responses. Nature, 2009, 458:351-357

3.    Liang Z. et al., TGFb-induced Foxp3 inhibits Th17 cell differentiation by antagonizing RORgt function. Nature, 2008, 453:236-241