Skin-resident innate lymphoid cells converge on a pathogenic effector state

BIELECKI, PIOTR; RIESENFELD, SAMANTHA J.; HÜTTER, JAN-CHRISTIAN; TORLAI TRIGLIA, ELENA; KOWALCZYK, MONIKA S.; RICARDO-GONZALEZ, ROBERTO R.; LIAN, MI; AMEZCUA VESELY, MARIA C.; KROEHLING, LINA; XU, HAO; SLYPER, MICHAL; MUUS, CHRISTOPH; LUDWIG, LEIF S.; CHRISTIAN, ELENA; TAO, LIMING; KEDAIGLE, AMANDA J.; STEACH, HOLLY R.; YORK, AUTUMN G.; SKADOW, MATHIAS H.; YAGHOUBI, PARASTOU; DIONNE, DANIELLE; JARRET, ABIGAIL; MCGEE, HEATHER M.; PORTER, CAROLINE B. M.; LICONA-LIMÓN, PAULA; BAILIS, WILL; JACKSON, RUAIDHRÍ; GAGLIANI, NICOLA; GASTEIGER, GEORG; LOCKSLEY, RICHARD M.; REGEV, AVIV; FLAVELL, RICHARD A.

NATURE

NATURE PUBLISHING GROUP

Año: 2021

0028-0836

issue-resident innate lymphoid cells (ILCs) help sustain barrier function and respond to local signals. ILCs are traditionally classified as ILC1, ILC2 or ILC3 on the basis of their expression of specific transcription factors and cytokines1. In the skin, disease-specific production of ILC3-associated cytokines interleukin (IL)-17 and IL-22 in response to IL-23 signalling contributes to dermal inflammation in psoriasis. However, it is not known whether this response is initiated by pre-committed ILCs or by cell-state transitions. Here we show that the induction of psoriasis in mice by IL-23 or imiquimod reconfigures a spectrum of skin ILCs, which converge on a pathogenic ILC3-like state. Tissue-resident ILCs were necessary and sufficient, in the absence of circulatory ILCs, to drive pathology. Single-cell RNA-sequencing (scRNA-seq) profiles of skin ILCs along a time course of psoriatic inflammation formed a dense transcriptional continuum?even at steady state?reflecting fluid ILC stat