title: Perturbed Mucosal Immunity and Dysbiosis Accompany Clinical Disease in a Rat Model of Spondyloarthritis.
abstract: The HLA-B27/β2 -microglobulin (β2 m)-transgenic (Tg) rat is a leading model of B27-associated spondyloarthritis (SpA), and the disease is dependent on the presence of intestinal bacteria. Previous studies have shown that adult HLA-B27/β2 m-Tg rats have an altered intestinal microbiota. This study sought to better define the age-dependent changes to both mucosal immune function and dysbiosis in this rat model of SpA.
  
  
  
  Intestinal contents were collected from wild-type and HLA-B27/β2 m-Tg rats postweaning (ages 3 and 6 weeks), at disease onset (age 10 weeks), and after the establishment of disease (ages ≥16 weeks). The microbial community structure was determined by 16S ribosomal RNA sequencing and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Mucosal and systemic Th1, Th17, and Treg cell responses were analyzed by flow cytometry, as was the frequency of IgA-coated intestinal bacteria. Intestinal expression of inflammatory cytokines and antimicrobial peptides (AMPs) was determined by qRT-PCR.
  
  
  
  An inflammatory cytokine signature and elevated AMP expression during the postweaning period preceded the development of clinical bowel inflammation and dysbiosis in HLA-B27/β2 m-Tg rats. An early and sustained expansion of the Th17 cell pool was specifically observed in the cecal and colonic mucosa of HLA-B27/β2 m-Tg rats. Strongly elevated intestinal colonization of Akkermansia muciniphila and an increased frequency of IgA-coated fecal bacteria were significantly associated with expression of HLA-B27 and arthritis development.
  
  
  
  HLA-B27/β2 m expression in this rat model renders the host hyperresponsive to microbial antigens from infancy. Early activation of innate immunity and expansion of a mucosal Th17 signature are soon followed by dysbiosis in HLA-B27/β2 m-Tg animals. The pathologic processes of perturbed mucosal immunity and dysbiosis strongly merit further study in both prediseased and diseased populations of patients with SpA.
authors.affiliation: Oregon Health & Science University, Portland.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Asquith
authors.affiliation: Oregon Health & Science University, Portland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Stauffer
authors.affiliation: Oregon Health & Science University, Portland.
authors.forename: Sean
authors.initials: S
authors.lastname: Davin
authors.affiliation: Oregon Health & Science University, Portland.
authors.forename: Claire
authors.initials: C
authors.lastname: Mitchell
authors.affiliation: Oregon Health & Science University and Casey Eye Institute, Portland.
authors.forename: Phoebe
authors.initials: P
authors.lastname: Lin
authors.affiliation: Oregon Health & Science University, Casey Eye Institute, and Devers Eye Institute, Portland.
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000276:immunology; D018928:Immunity, Mucosal; D051381:Rats; D055647:Rats, Transgenic; D025241:Spondylarthritis / Q000150:complications* / Q000276:immunology*
chemical_list: D015796:HLA-B27 Antigen