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IL 6Rα function in myeloid cells modulates the inflammatory response during irritant contact dermatitis
Author(s) -
Frempah Benjamin,
LuckettChastain Lerin R.,
Gallucci Randle M.
Publication year - 2019
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13984
Subject(s) - myeloid , immunology , chemokine , inflammation , cytokine , population , monocyte , medicine , chemistry , environmental health
Irritant contact dermatitis ( ICD ) is characterized by epidermal hyperplasia, infiltration of leucocytes into lesional skin and inflammatory cytokine release. The cellular infiltrate during ICD comprises primarily cells of the myeloid lineage. Our group has previously shown that the cytokine IL ‐6 confers a protective effect to lesional skin during ICD . How IL ‐6Rα function in myeloid cells is involved in the inflammatory response during ICD is, however, unknown. In the present study, utilizing a chemical model of ICD , it is shown that mice with a myeloid‐specific knockout of the IL ‐6Rα ( IL ‐6Rα Δmyeloid ) display an exaggerated inflammatory response to benzalkonium chloride ( BKC ) and Jet propellant‐8 ( JP 8) fuel, two well‐characterized irritants relative to littermate control. Results from immunohistochemical and flow cytometric analyses revealed that IL ‐6Rα Δmyeloid mouse skin displayed increased epidermal hyperplasia and inflammatory monocyte influx into lesional skin but lower numbers of resident macrophages relative to littermate controls after irritant exposure. Multiplex immunoassay revealed significantly higher levels of pro‐inflammatory cytokines IL ‐1α and TNF ‐α, but reduced expression of chemokine proteins including CCL 2‐5, CCL 7, CCL 11, CXCL 1 and CXCL 10 in IL ‐6Rα Δmyeloid mouse skin relative to littermate control following irritant exposure. These results highlight a previously unknown role of IL ‐6Rα function in myeloid cells in modulating the inflammatory response and myeloid population dynamics during ICD .