IL-10 and regulatory T cells cooperate in allergen-specific immunotherapy to ameliorate allergic asthma

Bohm L, Maxeiner J, Meyer-Martin H, Reuter S, Finotto S, Klein M, Schild H, Schmitt E, Bopp T, Taube C (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Journal of Immunology American Association of Immunologists

Publisher: American Association of Immunologists

Book Volume: 194

Pages Range: 887-97

Journal Issue: 3

DOI: 10.4049/jimmunol.1401612

Abstract

Human studies demonstrated that allergen-specific immunotherapy (IT) represents an effective treatment for allergic diseases. IT involves repeated administration of the sensitizing allergen, indicating a crucial contribution of T cells to its medicinal benefit. However, the underlying mechanisms of IT, especially in a chronic disease, are far from being definitive. In the current study, we sought to elucidate the suppressive mechanisms of IT in a mouse model of chronic allergic asthma. OVA-sensitized mice were challenged with OVA or PBS for 4 wk. After development of chronic airway inflammation, mice received OVA-specific IT or placebo alternately to airway challenge for 3 wk. To analyze the T cell-mediated mechanisms underlying IT in vivo, we elaborated the role of T-bet-expressing Th1 cells, T cell-derived IL-10, and Ag-specific thymic as well as peripherally induced Foxp3(+) regulatory T (Treg) cells. IT ameliorated airway hyperresponsiveness and airway inflammation in a chronic asthma model. Of note, IT even resulted in a regression of structural changes in the airways following chronic inhaled allergen exposure. Concomitantly, IT induced Th1 cells, Foxp3(+), and IL-10-producing Treg cells. Detailed analyses revealed that thymic Treg cells crucially contribute to the effectiveness of IT by promoting IL-10 production in Foxp3-negative T cells. Together with the peripherally induced Ag-specific Foxp3(+) Treg cells, thymic Foxp3(+) Treg cells orchestrate the curative mechanisms of IT. Taken together, we demonstrate that IT is effective in a chronic allergic disease and dependent on IL-10 and thymic as well as peripherally induced Ag-specific Treg cells.

Authors with CRIS profile

Susetta Neurath-Finotto Department of Molecular Pneumology

Involved external institutions

Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE) Leiden University Medical Center NL Netherlands (NL)

How to cite

APA:

Bohm, L., Maxeiner, J., Meyer-Martin, H., Reuter, S., Finotto, S., Klein, M.,... Taube, C. (2015). IL-10 and regulatory T cells cooperate in allergen-specific immunotherapy to ameliorate allergic asthma. Journal of Immunology, 194(3), 887-97. https://dx.doi.org/10.4049/jimmunol.1401612

MLA:

Bohm, Livia, et al. "IL-10 and regulatory T cells cooperate in allergen-specific immunotherapy to ameliorate allergic asthma." Journal of Immunology 194.3 (2015): 887-97.

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