title: CXCR3+ Regulatory T Cells Control TH1 Responses in Crescentic GN.
abstract: Chemokines and chemokine receptors are implicated in regulatory T cell (Treg) trafficking to sites of inflammation and suppression of excessive immune responses in inflammatory and autoimmune diseases; however, the specific requirements for Treg migration into the inflamed organs and the positioning of these cells within the tissue are incompletely understood. Here, we report that Tregs expressing the TH1-associated chemokine receptor CXCR3 are enriched in the kidneys of patients with ANCA-associated crescentic GN and colocalize with CXCR3(+) effector T cells. To investigate the functional role of CXCR3(+) Tregs, we generated mice that lack CXCR3 in Tregs specifically (Foxp3(eGFP-Cre) × Cxcr3(fl/fl)) and induced experimental crescentic GN. Treg-specific deletion of CXCR3 resulted in reduced Treg recruitment to the kidney and an overwhelming TH1 immune response, with an aggravated course of the nephritis that was reversible on anti-IFNγ treatment. Together, these findings show that a subset of Tregs expresses CXCR3 and thereby, acquires trafficking properties of pathogenic CXCR3(+) TH1 cells, allowing Treg localization and control of excessive TH1 responses at sites of inflammation.
authors.affiliation: III. Medizinische Klinik.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Paust
authors.affiliation: III. Medizinische Klinik.
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Riedel
authors.affiliation: III. Medizinische Klinik.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Krebs
authors.affiliation: III. Medizinische Klinik.
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Turner
authors.affiliation: III. Medizinische Klinik.
authors.forename: Silke R
authors.initials: SR
authors.lastname: Brix
authors.affiliation: III. Medizinische Klinik.
authors.forename: Sonja
authors.initials: S
authors.lastname: Krohn
authors.affiliation: Institut für Pathologie.
authors.forename: Joachim
authors.initials: J
authors.lastname: Velden
authors.affiliation: Institut für Pathologie.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wiech
authors.affiliation: III. Medizinische Klinik.
authors.forename: Anna
authors.initials: A
authors.lastname: Kaffke
authors.affiliation: III. Medizinische Klinik.
authors.forename: Anett
authors.initials: A
authors.lastname: Peters
authors.affiliation: III. Medizinische Klinik.
authors.forename: Sabrina B
authors.initials: SB
authors.lastname: Bennstein
authors.affiliation: III. Medizinische Klinik.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kapffer
authors.affiliation: III. Medizinische Klinik.
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyer-Schwesinger
authors.affiliation: Institut für Experimentelle Immunologie und Hepatologie, and.
authors.forename: Claudia
authors.initials: C
authors.lastname: Wegscheid
authors.affiliation: Institut für Experimentelle Immunologie und Hepatologie, and.
authors.forename: Gisa
authors.initials: G
authors.lastname: Tiegs
authors.affiliation: III. Medizinische Klinik.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Thaiss
authors.affiliation: Institut für Immunologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker
authors.affiliation: III. Medizinische Klinik.
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Steinmetz
authors.affiliation: III. Medizinische Klinik.
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
authors.affiliation: III. Medizinische Klinik, panzer@uke.uni-hamburg.de.
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
mesh_terms: D000818:Animals; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D054367:Receptors, CXCR3; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: C515187:CXCR3 protein, human; D054367:Receptors, CXCR3
keywords: CXCR3; GN; Tregs; trafficking