Beschreibung:
<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Hand eczema, which is frequently caused by delayed‐type allergy, is treated with 9‐<jats:italic>cis</jats:italic>‐retinoic acid (9cis<jats:styled-content style="fixed-case">RA</jats:styled-content>). However, knowledge on how 9cis<jats:styled-content style="fixed-case">RA</jats:styled-content> modulates skin immunity is sparse.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>As dendritic cells (<jats:styled-content style="fixed-case">DCs</jats:styled-content>) are central in the pathogenesis of contact allergy, we investigated 9cis<jats:styled-content style="fixed-case">RA</jats:styled-content> modulation of <jats:styled-content style="fixed-case">DC</jats:styled-content> function in murine contact hypersensitivity (<jats:styled-content style="fixed-case">CHS</jats:styled-content>).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>9cis<jats:styled-content style="fixed-case">RA</jats:styled-content>‐differentiated <jats:styled-content style="fixed-case">DCs</jats:styled-content> (9cis<jats:styled-content style="fixed-case">RA</jats:styled-content>‐<jats:styled-content style="fixed-case">DCs</jats:styled-content>) were analysed for phenotype and function. <jats:italic>In vivo</jats:italic> 9cis<jats:styled-content style="fixed-case">RA</jats:styled-content>‐<jats:styled-content style="fixed-case">DCs</jats:styled-content> were tested in the <jats:styled-content style="fixed-case">CHS</jats:styled-content> model.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>9cis<jats:styled-content style="fixed-case">RA</jats:styled-content> induces the differentiation of a distinct <jats:styled-content style="fixed-case">CD</jats:styled-content>103<jats:sup>−</jats:sup> <jats:styled-content style="fixed-case">CD</jats:styled-content>207<jats:sup>−</jats:sup> regulatory <jats:styled-content style="fixed-case">DC</jats:styled-content> phenotype. <jats:styled-content style="fixed-case">CD</jats:styled-content>11c<jats:sup>+</jats:sup> <jats:styled-content style="fixed-case">DCs</jats:styled-content> differentiated with 9cis<jats:styled-content style="fixed-case">RA</jats:styled-content> have lower expression of major histocompatibility complex‐<jats:styled-content style="fixed-case">II</jats:styled-content> and costimulatory molecules, but conversely have higher expression of the inhibitory coreceptor <jats:styled-content style="fixed-case">PD</jats:styled-content>1‐<jats:styled-content style="fixed-case">L</jats:styled-content>. 9cis<jats:styled-content style="fixed-case">RA</jats:styled-content>‐<jats:styled-content style="fixed-case">DC</jats:styled-content> culture does not induce the expression of proinflammatory cytokines, but strongly enhances osteopontin (<jats:styled-content style="fixed-case">OPN</jats:styled-content>) secretion. 9cis<jats:styled-content style="fixed-case">RA</jats:styled-content>‐<jats:styled-content style="fixed-case">DCs</jats:styled-content> are compromised in the induction of <jats:styled-content style="fixed-case">T</jats:styled-content> cell proliferation <jats:italic>in vitro</jats:italic>, but efficiently convert naive <jats:styled-content style="fixed-case">T</jats:styled-content> cells into regulatory <jats:styled-content style="fixed-case">T</jats:styled-content> cells (<jats:styled-content style="fixed-case">T</jats:styled-content>regs). Notably, <jats:styled-content style="fixed-case">OPN</jats:styled-content>‐deficient 9cis<jats:styled-content style="fixed-case">RA</jats:styled-content>‐<jats:styled-content style="fixed-case">DCs</jats:styled-content> show a loss of <jats:styled-content style="fixed-case">T</jats:styled-content>reg‐inducing function, which is re‐established by substituting <jats:styled-content style="fixed-case">OPN</jats:styled-content>. <jats:italic>In vivo</jats:italic>, in allergic mice, allergen‐primed 9cis<jats:styled-content style="fixed-case">RA</jats:styled-content>‐<jats:styled-content style="fixed-case">DCs</jats:styled-content> suppress allergic inflammation and induce <jats:styled-content style="fixed-case">T</jats:styled-content>reg accumulation in skin draining lymph nodes.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>This study describes 9cis<jats:styled-content style="fixed-case">RA</jats:styled-content>‐mediated differentiation of a distinct <jats:styled-content style="fixed-case">DC</jats:styled-content> phenotype that relies on <jats:styled-content style="fixed-case">OPN</jats:styled-content> for <jats:styled-content style="fixed-case">T</jats:styled-content>reg transformation and suppresses established <jats:styled-content style="fixed-case">CHS</jats:styled-content> through <jats:styled-content style="fixed-case">T</jats:styled-content>reg induction.</jats:p></jats:sec>