Antigen-specific Treg regulate Th17-mediated lung neutrophilic inflammation, B-cell recruitment and polymeric IgA and IgM levels in the airways.
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 airways, 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.
Jaffar
Zeina
Z
Center for Environmental Health Sciences, Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA. zeina.jaffar@umontana.edu
Ferrini
Maria E
ME
Girtsman
Teri A
TA
Roberts
Kevan
K
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D000941:Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D020381:Interleukin-17; C034639:polymeric IgA; D007371:Interferon-gamma; D010047:Ovalbumin