Basophils promote innate lymphoid cell responses in inflamed skin

TY - JOUR

T1 - Basophils promote innate lymphoid cell responses in inflamed skin

AU - Kim, Brian S.

AU - Wang, Kelvin

AU - Siracusa, Mark C.

AU - Saenz, Steven A.

AU - Brestoff, Jonathan R.

AU - Monticelli, Laurel A.

AU - Noti, Mario

AU - Wojno, Elia D.Tait

AU - Fung, Thomas C.

AU - Kubo, Masato

AU - Artis, David

N1 - Publisher Copyright: © 2014 by The American Association of Immunologists, Inc.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Type 2 inflammation underlies allergic diseases such as atopic dermatitis, which is characterized by the accumulation of basophils and group 2 innate lymphoid cells (ILC2s) in inflamed skin lesions. Although murine studies have demonstrated that cutaneous basophil and ILC2 responses are dependent on thymic stromal lymphopoietin, whether these cell populations interact to regulate the development of cutaneous type 2 inflammation is poorly defined. In this study, we identify that basophils and ILC2s significantly accumulate in inflamed human and murine skin and form clusters not observed in control skin. We demonstrate that murine basophil responses precede ILC2 responses and that basophils are the dominant IL-4-enhanced GFP-expressing cell type in inflamed skin. Furthermore, basophils and IL-4 were necessary for the optimal accumulation of ILC2s and induction of atopic dermatitis- like disease.We show that ILC2s express IL-4Ra and proliferate in an IL-4-dependent manner. Additionally, basophil-derived IL- 4 was required for cutaneous ILC2 responses in vivo and directly regulated ILC2 proliferation ex vivo. Collectively, these data reveal a previously unrecognized role for basophil-derived IL-4 in promoting ILC2 responses during cutaneous inflammation.

AB - Type 2 inflammation underlies allergic diseases such as atopic dermatitis, which is characterized by the accumulation of basophils and group 2 innate lymphoid cells (ILC2s) in inflamed skin lesions. Although murine studies have demonstrated that cutaneous basophil and ILC2 responses are dependent on thymic stromal lymphopoietin, whether these cell populations interact to regulate the development of cutaneous type 2 inflammation is poorly defined. In this study, we identify that basophils and ILC2s significantly accumulate in inflamed human and murine skin and form clusters not observed in control skin. We demonstrate that murine basophil responses precede ILC2 responses and that basophils are the dominant IL-4-enhanced GFP-expressing cell type in inflamed skin. Furthermore, basophils and IL-4 were necessary for the optimal accumulation of ILC2s and induction of atopic dermatitis- like disease.We show that ILC2s express IL-4Ra and proliferate in an IL-4-dependent manner. Additionally, basophil-derived IL- 4 was required for cutaneous ILC2 responses in vivo and directly regulated ILC2 proliferation ex vivo. Collectively, these data reveal a previously unrecognized role for basophil-derived IL-4 in promoting ILC2 responses during cutaneous inflammation.

UR - https://www.scopus.com/pages/publications/84907195502

UR - https://www.scopus.com/pages/publications/84907195502#tab=citedBy

U2 - 10.4049/jimmunol.1401307

DO - 10.4049/jimmunol.1401307

M3 - Article

C2 - 25156365

SN - 0022-1767

VL - 193

SP - 3717

EP - 3725

JO - Journal of Immunology

JF - Journal of Immunology

IS - 7

ER -