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Commensal microbiota influence systemic autoimmune responses

(2015) EMBO JOURNAL. 34(4). p.466-474
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
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.
Keywords
B-CELLS, T-CELLS, LT-BETA-R, CELL RESPONSES, LYMPHOTOXIN-BETA, PERIPHERAL LYMPHOID ORGANS, SEGMENTED FILAMENTOUS BACTERIA, systemic autoimmunity, commensal microbiota, antinuclear antibodies, TISSUES, MICE, EXPRESSION

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Citation

Please use this url to cite or link to this publication:

Chicago
Van Praet, Jens, Erin Donovan, Inge Vanassche, Michael Drennan, Fien Windels, Amélie Dendooven, Liesbeth Allais, et al. 2015. “Commensal Microbiota Influence Systemic Autoimmune Responses.” Embo Journal 34 (4): 466–474.
APA
Van Praet, Jens, Donovan, E., Vanassche, I., Drennan, M., Windels, F., Dendooven, A., Allais, L., et al. (2015). Commensal microbiota influence systemic autoimmune responses. EMBO JOURNAL, 34(4), 466–474.
Vancouver
1.
Van Praet J, Donovan E, Vanassche I, Drennan M, Windels F, Dendooven A, et al. Commensal microbiota influence systemic autoimmune responses. EMBO JOURNAL. 2015;34(4):466–74.
MLA
Van Praet, Jens, Erin Donovan, Inge Vanassche, et al. “Commensal Microbiota Influence Systemic Autoimmune Responses.” EMBO JOURNAL 34.4 (2015): 466–474. Print.
@article{6896065,
  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.},
  author       = {Van Praet, Jens and Donovan, Erin and Vanassche, Inge and Drennan, Michael and Windels, Fien and Dendooven, Am{\'e}lie and Allais, Liesbeth and Cuvelier, Claude and van de Loo, Fons and Norris, Paula S and Kruglov, Andrey A and Nedospasov, Sergei A and Rabot, Silvie 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},
  issn         = {0261-4189},
  journal      = {EMBO JOURNAL},
  language     = {eng},
  number       = {4},
  pages        = {466--474},
  title        = {Commensal microbiota influence systemic autoimmune responses},
  url          = {http://dx.doi.org/10.15252/embj.201489966},
  volume       = {34},
  year         = {2015},
}

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