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Commensal microbiota influence systemic autoimmune responses
Author(s) -
Van Praet Jens T,
Donovan Erin,
Vanassche Inge,
Drennan Michael B,
Windels Fien,
Dendooven Amélie,
Allais Liesbeth,
Cuvelier Claude A,
Loo Fons,
Norris Paula S,
Kruglov Andrey A,
Nedospasov Sergei A,
Rabot Sylvie,
Tito Raul,
Raes Jeroen,
GaboriauRouthiau Valerie,
CerfBensussan Nadine,
Van de Wiele Tom,
Eberl Gérard,
Ware Carl F,
Elewaut Dirk
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201489966
Subject(s) - medicine , library science , university hospital , rheumatology , family medicine , computer science
Antinuclear antibodies are a hallmark feature of generalized autoimmune diseases, including systemic lupus erythematosus and systemic sclerosis. However, the processes underlying the loss of tolerance against nuclear self‐constituents remain largely unresolved. Using mice deficient in lymphotoxin and Hox11, we report that approximately 25% of mice lacking secondary lymphoid organs spontaneously develop specific antinuclear antibodies. Interestingly, we find this phenotype is not caused by a defect in central tolerance. Rather, cell‐specific deletion and in vivo lymphotoxin blockade link these systemic autoimmune responses to the formation of gut‐associated lymphoid tissue in the neonatal period of life. We further demonstrate antinuclear antibody production is influenced by the presence of commensal gut flora, in particular increased colonization with segmented filamentous bacteria, and IL‐17 receptor signaling. Together, these data indicate that neonatal colonization of gut microbiota influences generalized autoimmunity in adult life.