Research ArticlesImmunology

TSLP Elicits IL-33–Independent Innate Lymphoid Cell Responses to Promote Skin Inflammation

Science Translational Medicine  30 Jan 2013:
Vol. 5, Issue 170, pp. 170ra16
DOI: 10.1126/scitranslmed.3005374

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Immune Cell Activity at the Skin Barrier

The skin acts like soft armor, protecting the body from disease and environmental insults. In atopic dermatitis (AD), this barrier is disrupted, leading to inflammation. The role of various immune cells in this chronic disease has not been clear. Now, Kim and colleagues identify a subset of innate lymphoid cells (ILCs) in both human and mouse skin that contribute to disease pathogenesis.

ILCs have been reported in inflamed nasal polyps in people, as well as in inflamed lungs in mice. Hypothesizing that they also play a role in skin inflammation, Kim et al. analyzed cells isolated from the skin tissue of healthy control subjects and from the lesions of AD patients. There were more Lin CD25+ IL-33R+ RORγt group 2 ILCs (ILC2s) in the lesions of AD patients. In healthy mouse skin, the authors identified a similar ILC2 population. AD in humans is linked to cytokines interleukin-33 (IL-33), IL-25, and thymic stromal lymphopoietin (TSLP) in the skin. To this end, the authors investigated in mice whether the ILC2s played a role in inflammation at the skin barrier and if they were dependent on these cytokines. In a mouse model of AD, Kim et al. noted that ILC2s were increased and that AD pathogenesis was initiated independently of adaptive immunity and RORγt+ cells (a marker of group 3 ILCs). The mechanism was also independent of IL-25 and IL-33—which are normally implicated in group 2 ILC responses—yet dependent on TSLP. Depletion of the ILCs attenuated AD-like dermatitis in mice.

Group 2 ILCs have not yet been described in skin barrier function in humans. In these studies, Kim and colleagues show that ILC2s are always present in healthy skin, but accumulate in AD lesions and function by a mechanism that contrasts what has been reported in lungs and intestine. Future functional studies will be needed for human ILC2s in skin inflammation, but these preliminary data in mice and humans suggest that targeting group 2 ILCs will be a viable target for treating AD and other allergic diseases.