title: CD4+Th2 cells are directly regulated by IL-10 during allergic airway inflammation.
abstract: Interleukin-10 (IL-10) is an important regulatory cytokine required to control allergy and asthma. IL-10-mediated regulation of T cell-mediated responses was previously thought to occur indirectly via antigen-presenting cells. However, IL-10 can act directly on regulatory T cells and T helper type 17 (Th17) cells. In the context of allergy, it is therefore unclear whether IL-10 can directly regulate T helper type 2 (Th2) cells and whether this is an important regulatory axis during allergic responses. We sought to determine whether IL-10 signaling in CD4+Th2 cells was an important mechanism of immune regulation during airway allergy. We demonstrate that IL-10 directly limits Th2 cell differentiation and survival in vitro and in vivo. Ablation of IL-10 signaling in Th2 cells led to enhanced Th2 cell survival and exacerbated pulmonary inflammation in a murine model of house dust mite allergy. Mechanistically, IL-10R signaling regulated the expression of several genes in Th2 cells, including granzyme B. Indeed, IL-10 increased granzyme B expression in Th2 cells and led to increased Th2 cell death, identifying an IL-10-regulated granzyme B axis in Th2 cells controlling Th2 cell survival. This study provides clear evidence that IL-10 exerts direct effects on Th2 cells, regulating the survival of Th2 cells and severity of Th2-mediated allergic airway inflammation.
authors.affiliation: The Laboratory of Allergy and Anti-Helminth Immunity, Mill Hill Laboratory, The Francis Crick Institute, London, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Coomes
authors.affiliation: The Laboratory of Allergy and Anti-Helminth Immunity, Mill Hill Laboratory, The Francis Crick Institute, London, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Kannan
authors.affiliation: The Laboratory of Allergy and Anti-Helminth Immunity, Mill Hill Laboratory, The Francis Crick Institute, London, UK.
authors.forename: V S
authors.initials: VS
authors.lastname: Pelly
authors.affiliation: The Laboratory of Allergy and Anti-Helminth Immunity, Mill Hill Laboratory, The Francis Crick Institute, London, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Entwistle
authors.affiliation: The Laboratory of Allergy and Anti-Helminth Immunity, Mill Hill Laboratory, The Francis Crick Institute, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Guidi
authors.affiliation: The Laboratory of Allergy and Anti-Helminth Immunity, Mill Hill Laboratory, The Francis Crick Institute, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Perez-Lloret
authors.affiliation: The Laboratory of Allergy and Anti-Helminth Immunity, Mill Hill Laboratory, The Francis Crick Institute, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Nikolov
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: W
authors.initials: W
authors.lastname: Müller
authors.affiliation: The Laboratory of Allergy and Anti-Helminth Immunity, Mill Hill Laboratory, The Francis Crick Institute, London, UK.
authors.forename: M S
authors.initials: MS
authors.lastname: Wilson
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology; D053701:Receptors, Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D039741:Antigens, Dermatophagoides; D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D053804:Granzymes