Protective role of commensal bacteria in Sjögren Syndrome

J Autoimmun. 2018 Sep;93:45-56. doi: 10.1016/j.jaut.2018.06.004. Epub 2018 Jun 20.

Abstract

CD25 knock-out (CD25KO) mice spontaneously develop Sjögren Syndrome (SS)-like inflammation. We investigated the role of commensal bacteria by comparing CD25KO mice housed in conventional or germ-free conditions. Germ-free CD25KO mice have greater corneal barrier dysfunction, lower goblet cell density, increased total lymphocytic infiltration score, increased expression of IFN-γ, IL-12 and higher a frequency of CD4+IFN-γ+ cells than conventional mice. CD4+ T cells isolated from female germ-free CD25KO mice adoptively transferred to naive immunodeficient RAG1KO recipients caused more severe Sjögren-like disease than CD4+ T cells transferred from conventional CD25KO mice. Fecal transplant in germ-free CD25KO mice reversed the spontaneous dry eye phenotype and decreased the generation of pathogenic CD4+IFN-γ+ cells. Our studies indicate that lack of commensal bacteria accelerates the onset and severity of dacryoadenitis and generates autoreactive CD4+T cells with greater pathogenicity in the CD25KO model, suggesting that the commensal bacteria or their metabolites products have immunoregulatory properties that protect exocrine glands in the CD25KO SS model.

Keywords: CD25KO; Dacryoadenitis; Dry eye; Fecal transplant; Germ-free; Microbiome; Sjögren Syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • Cornea / immunology*
  • Cornea / pathology
  • Dacryocystitis / genetics
  • Dacryocystitis / immunology
  • Dacryocystitis / microbiology*
  • Dacryocystitis / pathology
  • Disease Models, Animal
  • Fecal Microbiota Transplantation
  • Female
  • Gastrointestinal Microbiome / immunology
  • Gene Expression Regulation
  • Germ-Free Life
  • Goblet Cells / immunology
  • Goblet Cells / pathology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology*
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Interleukin-2 Receptor alpha Subunit / deficiency
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Lacrimal Apparatus / immunology*
  • Lacrimal Apparatus / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Permeability
  • Sjogren's Syndrome / genetics
  • Sjogren's Syndrome / immunology
  • Sjogren's Syndrome / microbiology*
  • Sjogren's Syndrome / pathology
  • Symbiosis / immunology*

Substances

  • Homeodomain Proteins
  • IFNG protein, mouse
  • Il2ra protein, mouse
  • Interleukin-2 Receptor alpha Subunit
  • RAG-1 protein
  • Interleukin-12
  • Interferon-gamma