IL-12 can alleviate Th17-mediated allergic lung inflammation through induction of pulmonary IL-10 expression

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Abstract

Interleukin (IL)-12 has been shown to suppress T helper type 2 (Th2)-induced pathogenesis that is associated with allergic asthma, largely through interferon (IFN)-γ production. We have recently shown that in the absence of T-bet, the major regulator of IFN-γ expression, allergic lung inflammation is primarily associated with IL-17-associated recruitment of neutrophils into the pulmonary tract of mice. In the absence of T-bet, exogenous IL-12 was still able to suppress neutrophilic infiltration and to diminish levels of IL-17, IL-23, and IL-23R, as well as retinoic acid-related orphan receptorγt, the transcriptional regulator of the Th17 pathway. The same effects were observed in T-bet-/- IFN-γ-/- double knockout mice, showing an IFN-γ-independent effect of IL-12 in this model. IL-10 expression in the lungs of T-bet-deficient mice was significantly increased after IL-12 treatment, and inoculation of anti-IL-10R mAb completely reversed the ability of IL-12 to suppress histological inflammation, recruitment of inflammatory cell subsets into the lung, bronchiole hyperresponsiveness, and IL-17 production. We conclude that Th17-mediated allergic lung inflammation that becomes dominant in the absence of effective IFN-γ signaling can be effectively suppressed by IL-12 through an IL-10-dependent mechanism. © 2010 Society for Mucosal Immunology.

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Durrant, D. M., & Metzger, D. W. (2010). IL-12 can alleviate Th17-mediated allergic lung inflammation through induction of pulmonary IL-10 expression. Mucosal Immunology, 3(3), 301–311. https://doi.org/10.1038/mi.2010.9

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