Details

Autor(en) / Beteiligte

• Zaheer, Mahira
• Wang, Changjun
• Bian, Fang
• Yu, Zhiyuan
• Hernandez, Humberto
• de Souza, Rodrigo G.
• Simmons, Ken T.
• Schady, Deborah
• Swennes, Alton G.
• Pflugfelder, Stephen C.
• Britton, Robert A.
• de Paiva, Cintia S.

Titel

Protective role of commensal bacteria in Sjögren Syndrome

Ist Teil von

• Journal of autoimmunity, 2018-09, Vol.93, p.45-56

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. •Germ-free (GF) environment worsens severity and accelerates the onset of autoimmunity in the CD25KO Sjögren Syndrome Model.•GF CD25KO mice have greater dry eye phenotype and greater frequency of CD4+IFN-γ+ cells than conventional CD25KO mice.•Adoptive transfer of GF CD25KO CD4+T cells causes more severe disease in Rag1KO recipients than conventional CD25KO T cells.•Fecal transplant in GF CD25KO mice ameliorates autoimmunity by decreasing generation of pathogenic CD4+IFN-γ+ cells.•Neutralization of IL-12 in GF CD25KO mice decreases the severity of dacryoadenitis.