Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells
In: Cell Reports, Jg. 42 (2023), Heft 3, S. 112193-
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Summary: Interleukin (IL)-10 is a main player in peripheral immune tolerance, the physiological mechanism preventing immune reactions to self/harmless antigens. Here, we investigate IL-10-induced molecular mechanisms generating tolerogenic dendritic cells (tolDC) from monocytes. Using genomic studies, we show that IL-10 induces a pattern of accessible enhancers exploited by aryl hydrocarbon receptor (AHR) to promote expression of a set of core genes. We demonstrate that AHR activity occurs downstream of IL-10 signaling in myeloid cells and is required for the induction of tolerogenic activities in DC. Analyses of circulating DCs show that IL-10/AHR genomic signature is active in vivo in health. In multiple sclerosis patients, we instead observe significantly altered signature correlating with functional defects and reduced frequencies of IL-10-induced-tolDC in vitro and in vivo. Our studies identify molecular mechanisms controlling tolerogenic activities in human myeloid cells and may help in designing therapies to re-establish immune tolerance.
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Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells
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Autor/in / Beteiligte Person: | Avancini, Daniele ; Testori, Alessandro ; Fresolone, Lucia ; Andolfi, Grazia ; Vuono, Michela ; Martinelli, Vittorio ; Francesca R. Santoni de Sio ; Gregori, Silvia |
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Zeitschrift: | Cell Reports, Jg. 42 (2023), Heft 3, S. 112193- |
Veröffentlichung: | Elsevier, 2023 |
Medientyp: | academicJournal |
ISSN: | 2211-1247 (print) |
DOI: | 10.1016/j.celrep.2023.112193 |
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