Type 2 cytokines: mechanisms and therapeutic strategies

Nat Rev Immunol. 2015 May;15(5):271-82. doi: 10.1038/nri3831. Epub 2015 Apr 17.


Type 2 immune responses are defined by the cytokines interleukin-4 (IL-4), IL-5, IL-9 and IL-13, which can either be host protective or have pathogenic activity. Type 2 immunity promotes antihelminth immunity, suppresses type 1-driven autoimmune disease, neutralizes toxins, maintains metabolic homeostasis, and regulates wound repair and tissue regeneration pathways following infection or injury. Nevertheless, when type 2 responses are dysregulated, they can become important drivers of disease. Type 2 immunity induces a complex inflammatory response characterized by eosinophils, mast cells, basophils, type 2 innate lymphoid cells, IL-4-and/or IL-13-conditioned macrophages and T helper 2 (TH2) cells, which are crucial to the pathogenesis of many allergic and fibrotic disorders. As chronic type 2 immune responses promote disease, the mechanisms that regulate their maintenance are thought to function as crucial disease modifiers. This Review discusses the many endogenous negative regulatory mechanisms that antagonize type 2 immunity and highlights how therapies that target some of these pathways are being developed to treat type 2-mediated disease.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Adaptive Immunity / immunology*
  • Basophils / immunology
  • Cytokines / immunology*
  • Eosinophils / immunology
  • Humans
  • Immunity, Innate / immunology*
  • Interleukin-13 / immunology
  • Interleukin-17 / immunology
  • Interleukin-4 / immunology
  • Interleukin-5 / immunology
  • Interleukin-9 / immunology
  • Mast Cells / immunology
  • Th2 Cells / immunology*


  • Cytokines
  • Interleukin-13
  • Interleukin-17
  • Interleukin-5
  • Interleukin-9
  • Interleukin-4
  • thymic stromal lymphopoietin