Antigen-specific Treg regulate Th17-mediated lung neutrophilic inflammation, B-cell recruitment and polymeric IgA and IgM levels in the airways

被引:38
作者
Jaffar, Zeina [1 ]
Ferrini, Maria E. [1 ]
Girtsman, Teri A. [1 ]
Roberts, Kevan [1 ]
机构
[1] Univ Montana, Ctr Environm Hlth Sci Biomed & Pharmaceut Sci, Missoula, MT 59812 USA
关键词
B cells; Lung inflammation; Regulation; Treg; Th17; cells; EFFECTOR T-CELLS; TGF-BETA; CUTTING EDGE; TH17; CELLS; EXPRESSION; RESPONSES; RECEPTOR; IL-17; INTERLEUKIN-17; DISTINCT;
D O I
10.1002/eji.200939498
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Th17 cells play key roles in mediating autoimmunity, inflammation and mucosal host defense against pathogens. To determine whether naturally occurring Treg (nTreg) limit Th17-mediated pulmonary inflammation, OVA-specific CD4(+) Th17 cells and expanded CD4(+)CD25(+)Foxp3(+) nTreg were cotransferred into BALB/c mice that were then exposed to OVA aerosols. Th17 cells, when transferred alone, accumulated in the lungs and posterior mediastinal LN and evoked a pronounced airway hyperreactivity and neutrophilic inflammation, characterized by B-cell recruitment and elevated IgA and IgM levels. Cotransfer of antigen-specific nTreg markedly reduced the Th17-induced pulmonary inflammation and associated neutrophilia, B-cell influx and polymeric Ig levels in the air-ways, but did not inhibit airway hyperreactivity. Moreover, the regulation appeared restricted to the site of mucosal inflammation, since transfer of nTreg did not affect the Th17 response developing in the lung draining LN, as evidenced by unaltered levels of IL-17 production and low numbers of Foxp3(+) Treg. Our findings suggest a crucial role for Th17 cells in mediating airway B-cell influx and IgA response, and demonstrate that antigen-specific nTreg suppress Th17-mediated lung inflammation. These results provide new insights into how Th17 responses are limited and may facilitate development of novel approaches for controlling Th17-induced inflammation.
引用
收藏
页码:3307 / 3314
页数:8
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