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9‐ cis ‐ R etinoic acid induces a distinct regulatory dendritic cell phenotype that modulates murine delayed‐type allergy
Author(s) -
Kraus LeaFranziska,
Scheurmann Natalie,
Frenzel Denis F.,
Tasdogan Alpaslan,
Weiss Johannes M.
Publication year - 2018
Publication title -
contact dermatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.524
H-Index - 96
eISSN - 1600-0536
pISSN - 0105-1873
DOI - 10.1111/cod.12868
Subject(s) - cd11c , immunology , dendritic cell , proinflammatory cytokine , retinoic acid , phenotype , siglec , microbiology and biotechnology , biology , inflammation , immune system , cell culture , biochemistry , genetics , gene
Summary 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 CD 103 − CD 207 − regulatory DC phenotype. CD 11c + 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 PD 1‐ 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 ( T regs). Notably, OPN ‐deficient 9cis RA ‐ DCs show a loss of T reg‐inducing function, which is re‐established by substituting OPN . In vivo , in allergic mice, allergen‐primed 9cis RA ‐ DCs suppress allergic inflammation and induce T reg accumulation in skin draining lymph nodes. Conclusions This study describes 9cis RA ‐mediated differentiation of a distinct DC phenotype that relies on OPN for T reg transformation and suppresses established CHS through T reg induction.