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. \copyright 2015 The Authors.
%0 Journal Article
%1 VanPraet2015Commensal
%A Van Praet, Jens T.
%A Donovan, Erin
%A Vanassche, Inge
%A Drennan, Michael B.
%A Windels, Fien
%A Dendooven, Amélie
%A Allais, Liesbeth
%A Cuvelier, Claude A.
%A van de Loo, Fons
%A Norris, Paula S.
%A Kruglov, Andrey A.
%A Nedospasov, Sergei A.
%A Rabot, Sylvie
%A Tito, Raul
%A Raes, Jeroen
%A Gaboriau-Routhiau, Valerie
%A Cerf-Bensussan, Nadine
%A Van de Wiele, Tom
%A Eberl, Gérard
%A Ware, Carl F.
%A Elewaut, Dirk
%D 2015
%J The EMBO journal
%K gut-microbiome immune-system
%T Commensal microbiota influence systemic autoimmune responses.
%U http://view.ncbi.nlm.nih.gov/pubmed/25599993
%X 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. \copyright 2015 The Authors.
@article{VanPraet2015Commensal,
abstract = {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. {\copyright} 2015 The Authors.},
added-at = {2018-12-02T16:09:07.000+0100},
author = {Van Praet, Jens T. and Donovan, Erin and Vanassche, Inge and Drennan, Michael B. and Windels, Fien and Dendooven, Am\'{e}lie and Allais, Liesbeth and Cuvelier, Claude A. and van de Loo, Fons and Norris, Paula S. and Kruglov, Andrey A. and Nedospasov, Sergei A. and Rabot, Sylvie and Tito, Raul and Raes, Jeroen and Gaboriau-Routhiau, Valerie and Cerf-Bensussan, Nadine and Van de Wiele, Tom and Eberl, G\'{e}rard and Ware, Carl F. and Elewaut, Dirk},
biburl = {https://www.bibsonomy.org/bibtex/2b8e2301c125e7df96bc00387f8013165/karthikraman},
citeulike-article-id = {13503223},
citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/25599993},
citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=25599993},
day = 19,
interhash = {c8970705231d3bdec4d140f70363d497},
intrahash = {b8e2301c125e7df96bc00387f8013165},
issn = {1460-2075},
journal = {The EMBO journal},
keywords = {gut-microbiome immune-system},
month = jan,
pmid = {25599993},
posted-at = {2015-01-28 16:18:18},
priority = {2},
timestamp = {2018-12-02T16:09:07.000+0100},
title = {Commensal microbiota influence systemic autoimmune responses.},
url = {http://view.ncbi.nlm.nih.gov/pubmed/25599993},
year = 2015
}