Elsevier

Mucosal Immunology

Volume 5, Issue 6, November 2012, Pages 670-680
Mucosal Immunology

Article
A role for mucosal IL-22 production and Th22 cells in HIV-associated mucosal immunopathogenesis

https://doi.org/10.1038/mi.2012.72Get rights and content
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Abstract

Interleukin-22 (IL-22) is a cytokine with epithelial reparative and regenerative properties that is produced by Th22 cells and by other immune cell subsets. Therefore, we explored the hypothesis that disruption of the gut barrier during HIV infection involves dysregulation of these cells in the gastrointestinal mucosa. Sigmoid IL-22-producing T cell and Th22 cells were dramatically depleted during chronic HIV infection, epithelial integrity was compromised, and microbial translocation was increased. These alterations were reversed after long-term antiretroviral therapy. While all mucosal IL-22-producing T-cell subsets were also depleted very early during HIV infection, at these early stages IL-22 production by non-T-cell populations (including NKp44+ cells) was increased and gut epithelial integrity was maintained. Circulating Th22 cells expressed a higher level of the HIV co-receptor/binding molecules CCR5 and α4β7 than CD4+ T-cell subsets in HIV-uninfected participants, but this was not the case after HIV infection. Finally, recombinant IL-22 was protective against HIV and tumor necrosis factor-α-induced gut epithelial damage in a validated in vitro gut epithelial system. We conclude that reduced IL-22 production and Th22 depletion in the gut mucosa are important factors in HIV mucosal immunopathogenesis.

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Published online: 1 8 2012

SUPPLEMENTARY MATERIAL is linked to the online version of the paper

Supplementary information The online version of this article (doi:10.1038/mi.2012.72) contains supplementary material, which is available to authorized users.