A tissue checkpoint regulates type 2 immunity

Nat Immunol. 2016 Dec;17(12):1381-1387. doi: 10.1038/ni.3582. Epub 2016 Oct 17.


Group 2 innate lymphoid cells (ILC2s) and CD4+ type 2 helper T cells (TH2 cells) are defined by their similar effector cytokines, which together mediate the features of allergic immunity. We found that tissue ILC2s and TH2 cells differentiated independently but shared overlapping effector function programs that were mediated by exposure to the tissue-derived cytokines interleukin 25 (IL-25), IL-33 and thymic stromal lymphopoietin (TSLP). Loss of these three tissue signals did not affect lymph node priming, but abrogated the terminal differentiation of effector TH2 cells and adaptive lung inflammation in a T cell-intrinsic manner. Our findings suggest a mechanism by which diverse perturbations can activate type 2 immunity and reveal a shared local-tissue-elicited checkpoint that can be exploited to control both innate and adaptive allergic inflammation.

MeSH terms

  • Adaptive Immunity
  • Allergens / immunology
  • Animals
  • Aspergillus niger
  • Bee Venoms / immunology
  • Bees
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Dermatophagoides farinae
  • Hypersensitivity / immunology*
  • Immunity, Innate*
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Interleukin-33 / genetics
  • Interleukin-33 / metabolism*
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Th2 Cells / immunology*


  • Allergens
  • Bee Venoms
  • Cytokines
  • IL25 protein, human
  • Interleukin-17
  • Interleukin-33
  • thymic stromal lymphopoietin