title: Enteric mucosa integrity in the presence of a preserved innate interleukin 22 compartment in HIV type 1-treated individuals.
abstract: BACKGROUND
  Interleukin 22 (IL-22) is emerging as a key cytokine for gut epithelial homeostasis and mucosal repair. Gut disruption is a hallmark of human immunodeficiency virus (HIV) infection. Here, we investigated IL-22 production and gut mucosal integrity in HIV type 1 (HIV-1)-infected individuals receiving long-term antiretroviral therapy (ART).
  
  
  METHODS
  Biopsy specimens from 37 individuals who underwent colonoscopy primarily for cancer screening and from 17 HIV-1-infected and 20 healthy age-matched controls were assessed.
  
  
  RESULTS
  We found significant depletion of sigmoid IL-22-producing CD4(+) T cells (T-helper type 22 [Th22] cells) even after prolonged ART, contrasting with the apparently normal compartments of regulatory and interleukin 17 (IL-17)-producing CD4(+) T cells, as well as total mucosal CD4(+) T cells. Despite the preferential Th22 cell depletion, IL-22 production by innate lymphoid cells (ILCs) was similar to that observed in HIV-1-seronegative subjects, and transcription of genes encoding molecules relevant for IL-22 production (ie, AHR, IL23, IL23R, IL1B, IL6, and TGFB1) was preserved. Remarkably, levels of transcripts of IL-22-target genes (ie, REG3G, DEFB4A, S100A9, MUC1, and MUC13) were unaltered, suggesting an adequate production of antimicrobial peptides and mucins. In agreement, enteric epithelial architecture was fully preserved.
  
  
  CONCLUSIONS
  Despite the reduced Th22 cell subset, innate IL-22-mediated mechanisms, essential for sigmoid mucosa integrity, were fully operational in long-term-treated HIV-1-infected individuals. Our data highlight IL-22 production by ILCs as an important target for therapies aimed at facilitating human mucosal reconstitution.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa Clínica Universitária de Medicina II.
authors.forename: Susana M
authors.initials: SM
authors.lastname: Fernandes
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Pires
authors.affiliation: Serviço de Anatomia Patológica.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ferreira
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa.
authors.forename: Russell B
authors.initials: RB
authors.lastname: Foxall
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa.
authors.forename: José
authors.initials: J
authors.lastname: Rino
authors.affiliation: Clínica Universitária de Doenças Infecciosas.
authors.forename: Carla
authors.initials: C
authors.lastname: Santos
authors.affiliation: Clínica Universitária de Gastroenterologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte-EPE, Lisboa.
authors.forename: Luís
authors.initials: L
authors.lastname: Correia
authors.affiliation: Serviço de Infecciologia, Hospital de S. Bernardo, Setúbal, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Poças
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa.
authors.forename: Henrique
authors.initials: H
authors.lastname: Veiga-Fernandes
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa.
authors.forename: Ana E
authors.initials: AE
authors.lastname: Sousa
mesh_terms: D000368:Aged; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014158:Transcription, Genetic / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D000097043:Interleukin-22
keywords: HIV/AIDS; IL-22; antiretroviral therapy; gut associated lymphoid tissue; mucosa reconstitution