title: Intestinal bacteria induce TSLP to promote mutualistic T-cell responses.
abstract: Thymic stromal lymphopoietin (TSLP) is constitutively expressed in the intestine and is known to regulate inflammation in models of colitis. We show that steady-state TSLP expression requires intestinal bacteria and has an important role in limiting the expansion of colonic T helper type 17 (Th17) cells. Inappropriate expansion of the colonic Th17 cells occurred in response to an entirely benign intestinal microbiota, as determined following the colonization of germ-free C57BL/6 or TSLPR(-/-) mice with the altered Schaedler flora (ASF). TSLP-TSLPR (TSLP receptor) interactions also promoted the expansion of colonic Helios(-)Foxp3(+) regulatory T cells, necessary for the control of inappropriate Th17 responses following ASF bacterial colonization. In summary, these data reveal an important role for TSLP-TSLPR signaling in promoting steady-state mutualistic T-cell responses following intestinal bacterial colonization.
authors.affiliation: Swiss Vaccine Research Institute and Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Mosconi
authors.forename: M B
authors.initials: MB
authors.lastname: Geuking
authors.forename: M M
authors.initials: MM
authors.lastname: Zaiss
authors.forename: J C
authors.initials: JC
authors.lastname: Massacand
authors.forename: C
authors.initials: C
authors.lastname: Aschwanden
authors.forename: C K C
authors.initials: CK
authors.lastname: Kwong Chung
authors.forename: K D
authors.initials: KD
authors.lastname: McCoy
authors.forename: N L
authors.initials: NL
authors.lastname: Harris
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology*; D002450:Cell Communication; D049109:Cell Proliferation; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D007136:Immunoglobulins / Q000378:metabolism; D056747:Immunomodulation; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota / Q000276:immunology; D018121:Receptors, Cytokine / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007136:Immunoglobulins; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse; D000094632:Thymic Stromal Lymphopoietin