TY - JOUR
T1 - TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation
AU - Kim, Brian S.
AU - Siracusa, Mark C.
AU - Saenz, Steven A.
AU - Noti, Mario
AU - Monticelli, Laurel A.
AU - Sonnenberg, Gregory F.
AU - Hepworth, Matthew R.
AU - Van Voorhees, Abby S.
AU - Comeau, Michael R.
AU - Artis, David
PY - 2013/1/30
Y1 - 2013/1/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84874055169&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.3005374
DO - 10.1126/scitranslmed.3005374
M3 - Article
C2 - 23363980
AN - SCOPUS:84874055169
SN - 1946-6234
VL - 5
JO - Science translational medicine
JF - Science translational medicine
IS - 170
M1 - 170ra16
ER -