| Autor: |
Kerry L Hilligan, Luis Munoz-Erazo, Lisa M Connor, Sally Chappell, Alan Sher, Franca Ronchese, Charles R. Mackay, Olivier Lamiable, Graham Le Gros, Jianping Yang, Dragana Jankovic, Kirsty A. Wakelin, Matthew R. Hepworth, David Eccles, Greta R Webb, Frank Brombacher, Evelyn J Hyde, Jodie Chandler, Samuel I Old, Roxane Tussiwand, Rita G. Domingues, Johannes U Mayer, Shiau-Choot Tang |
| Rok vydání: |
2021 |
| Předmět: |
|
| Popis: |
The signals driving the adaptation of type-2 dendritic cells (DC2s) to diverse peripheral environments are not well understood. We show that the development of CD11blow migratory DC2s, a DC2 population unique to the dermis, requires STAT6- and KLF4-dependent IL-13 signaling, whereas DC2s in lung and small intestine are STAT6-independent. Dermal IL-13 is mostly derived from innate lymphoid cells expressing a resting ICOS+ KLRG1-ST2-phenotype. Analysis of public datasets indicates that human skin DC2s also express an IL-4/IL-13 gene signature compared to blood or spleen, suggesting a similar developmental pathway in mice and humans. In the absence of IL-13 signaling, dermal DC2s are stable in number but remain CD11bhi and show defective activation in response to allergen with diminished ability to support IL-4+ GATA3+ Th development, whereas anti-fungal IL-17+ RORγt+ responses are increased. Thus, steady-state IL-13 fosters a non-inflammatory and pro-allergic environment in healthy skin via conditioning of local DC2s. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
