TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation

Sci Transl Med. 2013 Jan 30;5(170):170ra16. doi: 10.1126/scitranslmed.3005374.

Abstract

Innate lymphoid cells (ILCs) are a recently identified family of heterogeneous immune cells that can be divided into three groups based on their differential developmental requirements and expression of effector cytokines. Among these, group 2 ILCs produce the type 2 cytokines interleukin-5 (IL-5) and IL-13 and promote type 2 inflammation in the lung and intestine. However, whether group 2 ILCs reside in the skin and contribute to skin inflammation has not been characterized. We identify a population of skin-resident group 2 ILCs present in healthy human skin that are enriched in lesional human skin from atopic dermatitis (AD) patients. Group 2 ILCs were also found in normal murine skin and were critical for the development of inflammation in a murine model of AD-like disease. Remarkably, in contrast to group 2 ILC responses in the intestine and lung, which are critically regulated by IL-33 and IL-25, group 2 ILC responses in the skin and skin-draining lymph nodes were independent of these canonical cytokines but were critically dependent on thymic stromal lymphopoietin (TSLP). Collectively, these results demonstrate an essential role for IL-33- and IL-25-independent group 2 ILCs in promoting skin inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Cytokines / metabolism*
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / pathology
  • Disease Models, Animal
  • Humans
  • Immunity, Innate / immunology*
  • Inflammation / immunology*
  • Inflammation / pathology
  • Interleukin-33
  • Interleukins / metabolism*
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Protein Binding
  • Skin / immunology
  • Skin / pathology*

Substances

  • Cytokines
  • IL33 protein, human
  • Il33 protein, mouse
  • Interleukin-33
  • Interleukins
  • thymic stromal lymphopoietin