title: Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses.
abstract: Foxp3(+) T regulatory (Treg) cells regulate immune responses and maintain self-tolerance. Recent work shows that Treg cells are comprised of many subpopulations with specialized regulatory functions. Here we identified Foxp3(+) T cells expressing the coinhibitory molecule TIGIT as a distinct Treg cell subset that specifically suppresses proinflammatory T helper 1 (Th1) and Th17 cell, but not Th2 cell responses. Transcriptional profiling characterized TIGIT(+) Treg cells as an activated Treg cell subset with high expression of Treg signature genes. Ligation of TIGIT on Treg cells induced expression of the effector molecule fibrinogen-like protein 2 (Fgl2), which promoted Treg-cell-mediated suppression of T effector cell proliferation. In addition, Fgl2 was necessary to prevent suppression of Th2 cytokine production in a model of allergic airway inflammation. TIGIT expression therefore identifies a Treg cell subset that demonstrates selectivity for suppression of Th1 and Th17 cell but not Th2 cell responses.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Joller
authors.affiliation: Department of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Ester
authors.initials: E
authors.lastname: Lozano
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Burkett
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bonny
authors.initials: B
authors.lastname: Patel
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Junrong
authors.initials: J
authors.lastname: Xia
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Tze G
authors.initials: TG
authors.lastname: Tan
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Esen
authors.initials: E
authors.lastname: Sefik
authors.affiliation: Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Yajnik
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Quintana
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.affiliation: Department of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: vkuchroo@rics.bwh.harvard.edu.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology; D005340:Fibrinogen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058408:Th1-Th2 Balance
chemical_list: D016207:Cytokines; C490637:Fgl2 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011971:Receptors, Immunologic; C556305:T cell Ig and ITIM domain protein, mouse; D005340:Fibrinogen
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