Basophils promote innate lymphoid cell responses in inflamed skin.

Abstract

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-4Rα 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.

• Authors: Brian S Kim, Kelvin Wang, Mark C Siracusa, Steven A Saenz, Jonathan R Brestoff, Laurel A Monticelli, Mario Noti, Elia D Tait Wojno, Thomas C Fung, Masato Kubo, David Artis
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 193 Issue 7 Pg. 3717-25 (Oct 01 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 25156365 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2014 by The American Association of Immunologists, Inc.

Chemical References

• Cytokines
• IL4 protein, human
• Il4ra protein, mouse
• Receptors, Cell Surface
• Interleukin-4
• Thymic Stromal Lymphopoietin

Topics

• Animals
• Basophils (immunology, pathology)
• Cell Proliferation
• Cytokines (genetics, immunology)
• Dermatitis, Atopic (genetics, immunology, pathology)
• Female
• Humans
• Immunity, Innate
• Inflammation (genetics, immunology, pathology)
• Interleukin-4 (genetics, immunology)
• Lymphocytes (immunology, pathology)
• Male
• Mice
• Mice, Knockout
• Receptors, Cell Surface (genetics, immunology)
• Skin (immunology, pathology)
• Thymic Stromal Lymphopoietin