9- cis- Retinoic acid induces a distinct regulatory dendritic cell phenotype that modulates murine delayed-type allergy.

Autor: Kraus, Lea‐Franziska, Scheurmann, Natalie, Frenzel, Denis F., Tasdogan, Alpaslan, Weiss, Johannes M.
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Zdroj: Contact Dermatitis (01051873); Jan2018, Vol. 78 Issue 1, p41-54, 14p
Abstrakt: Background Hand eczema, which is frequently caused by delayed-type allergy, is treated with 9- cis-retinoic acid (9cis RA). However, knowledge on how 9cis RA modulates skin immunity is sparse. Objective As dendritic cells ( DCs) are central in the pathogenesis of contact allergy, we investigated 9cis RA modulation of DC function in murine contact hypersensitivity ( CHS). Methods 9cis RA-differentiated DCs (9cis RA- DCs) were analysed for phenotype and function. In vivo 9cis RA- DCs were tested in the CHS model. Results 9cis RA induces the differentiation of a distinct CD103− CD207− regulatory DC phenotype. CD11c+ DCs differentiated with 9cis RA have lower expression of major histocompatibility complex- II and costimulatory molecules, but conversely have higher expression of the inhibitory coreceptor PD1- L. 9cis RA- DC culture does not induce the expression of proinflammatory cytokines, but strongly enhances osteopontin ( OPN) secretion. 9cis RA- DCs are compromised in the induction of T cell proliferation in vitro, but efficiently convert naive T cells into regulatory T cells ( Tregs). Notably, OPN-deficient 9cis RA- DCs show a loss of Treg-inducing function, which is re-established by substituting OPN. In vivo, in allergic mice, allergen-primed 9cis RA- DCs suppress allergic inflammation and induce Treg accumulation in skin draining lymph nodes. Conclusions This study describes 9cis RA-mediated differentiation of a distinct DC phenotype that relies on OPN for Treg transformation and suppresses established CHS through Treg induction. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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