6533b861fe1ef96bd12c4fea

RESEARCH PRODUCT

Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation

Michael N. HedrickBjörn E. ClausenHoward ZhangPeter WolfTej Pratap SinghJoshua M. FarberBrian L. KelsallIzabela BorekSatya P. Singh

subject

0301 basic medicineSciencePopulationGeneral Physics and Astronomychemical and pharmacologic phenomenaInflammationInterleukin-23ArticleMonocytesGeneral Biochemistry Genetics and Molecular BiologyProinflammatory cytokineMajor Histocompatibility ComplexMice03 medical and health sciencesAdjuvants ImmunologicPsoriasismedicineInterleukin 23AnimalsHumansPsoriasiseducationSkinInflammationMice Knockouteducation.field_of_studyImiquimodMultidisciplinaryFollicular dendritic cellsbusiness.industryMonocyteQMembrane Proteinshemic and immune systemsDendritic CellsGeneral ChemistryTLR7medicine.disease3. Good health030104 developmental biologymedicine.anatomical_structureGene Expression RegulationLangerhans CellsImmunologyAminoquinolinesDrug Eruptionsmedicine.symptombusiness

description

Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6Chi blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod. Moreover, we find that IL-23-induced inflammation requires expression of CCR6 by DCs or their precursors, and that CCR6 mediates monocyte trafficking into inflamed skin. Collectively, our results imply that monocyte-derived cells are critical contributors to psoriasis through production of inflammatory cytokines that augment the activation of skin T cells.

yearjournalcountryeditionlanguage
2016-12-01Nature Communications
https://doi.org/10.1038/ncomms13581