title: A Distinct Function of Regulatory T Cells in Tissue Protection.
abstract: Regulatory T (Treg) cells suppress immune responses to a broad range of non-microbial and microbial antigens and indirectly limit immune inflammation-inflicted tissue damage by employing multiple mechanisms of suppression. Here, we demonstrate that selective Treg cell deficiency in amphiregulin leads to severe acute lung damage and decreased blood oxygen concentration during influenza virus infection without any measureable alterations in Treg cell suppressor function, antiviral immune responses, or viral load. This tissue repair modality is mobilized in Treg cells in response to inflammatory mediator IL-18 or alarmin IL-33, but not by TCR signaling that is required for suppressor function. These results suggest that, during infectious lung injury, Treg cells have a major direct and non-redundant role in tissue repair and maintenance-distinct from their role in suppression of immune responses and inflammation-and that these two essential Treg cell functions are invoked by separable cues.
authors: Howard Hughes Medical Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Nicholas
authors: N
authors: Arpaia
authors: Howard Hughes Medical Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Jesse A
authors: JA
authors: Green
authors: Howard Hughes Medical Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Bruno
authors: B
authors: Moltedo
authors: Howard Hughes Medical Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Aaron
authors: A
authors: Arvey
authors: Howard Hughes Medical Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Saskia
authors: S
authors: Hemmers
authors: Howard Hughes Medical Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; The David Rockefeller Graduate Program, The Rockefeller University, New York, NY 10065, USA.
authors: Shaopeng
authors: S
authors: Yuan
authors: Department of Comparative Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Piper M
authors: PM
authors: Treuting
authors: Howard Hughes Medical Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: rudenska@mskcc.org.
authors: Alexander Y
authors: AY
authors: Rudensky
mesh_terms: D066258:Amphiregulin / Q000235:genetics; D000818:Animals; D015551:Autoimmunity; D004195:Disease Models, Animal; D006801:Humans; D007251:Influenza, Human / Q000276:immunology* / Q000473:pathology; D008168:Lung / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D013491:Suppressor Factors, Immunologic / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000166:cytology* / Q000276:immunology*
chemical_list: D066258:Amphiregulin; D013491:Suppressor Factors, Immunologic