ILC2 activation by keratinocyte-derived IL-25 drives IL-13 production at sites of allergic skin inflammation - 08/06/20
, Claire Galand, PhD a, ∗, Shunya Mashiko, PhD b, Robert Bissonnette, MD c, Alex McGurk, BA a, Steven F. Ziegler, PhD d, e, Chen Dong, PhD f, g, Andrew N.J. McKenzie, PhD h, Marika Sarfati, MD, PhD b, Raif S. Geha, MD a, ⁎ Abstract |
Background |
Atopic dermatitis skin lesions demonstrate increased expression of IL-25 by keratinocytes and increased numbers of type 2 innate lymphoid cells (ILC2s) that express high levels of IL-25 receptor (IL-25R). IL-13 is expressed in atopic dermatitis skin lesions and plays an important role in pathogenesis of the disease.
Objective |
Our aim was to determine the role of IL-25 and ILC2s in a mouse model of antigen-driven allergic skin inflammation.
Methods |
Wild-type mice; mice that express an Il13-driven enhanced green fluorescent protein; and mice that lack IL-25R, IL-25 in keratinocytes, or IL-13 or IL-25R in ILC2s were subjected to acute or chronic epicutaneous sensitization with ovalbumin. Sensitized skin was examined by histology for epidermal thickening. Cellular infiltrates were analyzed for surface markers and intracellular expression of enhanced green fluorescent protein by flow cytometry. Gene expression was quantitated by RT quantitative PCR.
Result |
In both acute and chronic antigen-driven allergic skin inflammation, signaling by keratinocyte-derived IL-25 in ILC2s is important for epidermal hyperplasia, dermal infiltration by CD4+ T cells, and cutaneous expression of Il13 and the IL-13–dependent TH2-cell–attracting chemokines Cc17 and Ccl22. ILCs are the major source of IL-13 in acutely sensitized mouse skin, whereas T cells are its major source in chronically sensitized mouse skin.
Conclusion |
ILC2 activation by IL-25 is essential for IL-13 expression at sites of allergic skin inflammation.
Il testo completo di questo articolo è disponibile in PDF.Graphical abstract |
Key words : Atopic dermatitis, IL-25, IL-13, ILC2
Abbreviations used : AD, eGFP, IL-25R, ILC, ILC2, MC, TEWL, TSLP, WT
Mappa
| Funded by the National Institutes of Health/National Institute of Allergy and Infectious Diseases Atopic Dermatitis Research Network (grant U19AI117673); the National Institutes of Health (grant AI113294-01A1); and the National Institute of Allergy and Infectious Diseases (T32 training grant 5T32AI007512-32). |
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| Disclosure of potential conflict of interest: J. M. Leyva-Castillo was supported by a postdoctoral fellowship from Consejo Nacional de Ciencia y Tecnología (Mexico) and a Boston Children’s Hospital Office of Faculty Development/Basic/Translational Research Executive Committee (BTREC) and the Clinical and Translational Research Executive Committee (CTREC) Faculty Career Development Fellowship. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 145 - N° 6
P. 1606 - Giugno 2020 Ritorno al numero
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