title: A role for mucosal IL-22 production and Th22 cells in HIV-associated mucosal immunopathogenesis.
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.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada. kim.connie@gmail.com
authors.forename: C J
authors.initials: CJ
authors.lastname: Kim
authors.forename: A
authors.initials: A
authors.lastname: Nazli
authors.forename: O L
authors.initials: OL
authors.lastname: Rojas
authors.forename: D
authors.initials: D
authors.lastname: Chege
authors.forename: Z
authors.initials: Z
authors.lastname: Alidina
authors.forename: S
authors.initials: S
authors.lastname: Huibner
authors.forename: S
authors.initials: S
authors.lastname: Mujib
authors.forename: E
authors.initials: E
authors.lastname: Benko
authors.forename: C
authors.initials: C
authors.lastname: Kovacs
authors.forename: L Y Y
authors.initials: LY
authors.lastname: Shin
authors.forename: A
authors.initials: A
authors.lastname: Grin
authors.forename: G
authors.initials: G
authors.lastname: Kandel
authors.forename: M
authors.initials: M
authors.lastname: Loutfy
authors.forename: M
authors.initials: M
authors.lastname: Ostrowski
authors.forename: J L
authors.initials: JL
authors.lastname: Gommerman
authors.forename: C
authors.initials: C
authors.lastname: Kaushic
authors.forename: R
authors.initials: R
authors.lastname: Kaul
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D019070:Cell Lineage; D012809:Colon, Sigmoid / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D018928:Immunity, Mucosal; D007378:Interleukins / Q000172:deficiency / Q000276:immunology* / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology / Q000821:virology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D019713:Receptors, CCR5 / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology; D000097043:Interleukin-22
chemical_list: D019380:Anti-HIV Agents; D007378:Interleukins; D019713:Receptors, CCR5; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22