CCL2‒CCR2 Signaling in the Skin Drives Surfactant-Induced Irritant Contact Dermatitis through IL-1β‒Mediated Neutrophil Accumulation.

The Journal of Investigative Dermatology
Rintaro ShibuyaKenji Kabashima

Abstract

Surfactant-induced cumulative irritant contact dermatitis (ICD) is a common and clinically important skin disorder. CCL2 is known to mediate inflammation after tissue damage in various organs. Thus, we investigated whether and how CCL2 contributes to the development of murine cumulative ICD induced by a common surfactant, SDS. Wild-type mice treated topically with SDS for 6 consecutive days developed skin inflammation that recapitulated the features of human cumulative ICD, including barrier disruption, epidermal thickening, and neutrophil accumulation. CCL2 was upregulated in SDS-treated skin, and local CCL2 blockade attenuated SDS-induced ICD. SDS-induced ICD and neutrophil accumulation were also attenuated in mice deficient in CCR2, the receptor for CCL2. Neutrophil depletion alleviated SDS-induced ICD, suggesting that impaired neutrophil accumulation was responsible for the amelioration of ICD in CCR2-deficient mice. In RNA-sequencing analyses of SDS-treated skin, the expression levels of Il1b in Ccr2-deficient mice were highly downregulated compared with those in wild-type mice. Furthermore, the intradermal administration of IL-1β in the SDS-treated skin of CCR2-deficient mice restored the local accumulation of neutrophils...Continue Reading

References

Mar 1, 1987·The Journal of Investigative Dermatology·E PatrickH I Maibach
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Apr 5, 2016·Nature Biotechnology·Nicolas L BrayLior Pachter
Jun 6, 2017·Nature Methods·Harold PimentelLior Pachter

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