Background: Hand eczema, which is frequently caused by delayed-type allergy, is treated with 9-cis-retinoic acid (9cisRA). However, knowledge on how 9cisRA modulates skin immunity is sparse.
Objective: As dendritic cells (DCs) are central in the pathogenesis of contact allergy, we investigated 9cisRA modulation of DC function in murine contact hypersensitivity (CHS).
Methods: 9cisRA-differentiated DCs (9cisRA-DCs) were analysed for phenotype and function. In vivo 9cisRA-DCs were tested in the CHS model.
Results: 9cisRA induces the differentiation of a distinct CD103- CD207- regulatory DC phenotype. CD11c+ DCs differentiated with 9cisRA have lower expression of major histocompatibility complex-II and costimulatory molecules, but conversely have higher expression of the inhibitory coreceptor PD1-L. 9cisRA-DC culture does not induce the expression of proinflammatory cytokines, but strongly enhances osteopontin (OPN) secretion. 9cisRA-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 9cisRA-DCs show a loss of Treg-inducing function, which is re-established by substituting OPN. In vivo, in allergic mice, allergen-primed 9cisRA-DCs suppress allergic inflammation and induce Treg accumulation in skin draining lymph nodes.
Conclusions: This study describes 9cisRA-mediated differentiation of a distinct DC phenotype that relies on OPN for Treg transformation and suppresses established CHS through Treg induction.
Keywords: 9-cis-retinoic acid; contact hypersensitivity; dendritic cells; eczema; osteopontin; regulatory T cells; tolerance.
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.