Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 141, Issue 8, Pages 1995-+Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2021.01.013
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Funding
- National Institutes of Health [R01AR067751, R01AI127389]
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The study found that IL-10(+) Bregs in the skin play a crucial role in suppressing skin inflammation, as a decrease in IL-10(+) Bregs entering the skin leads to exacerbation of inflammation.
Pro and anti-inflammatory B-cell subsets that localize to unperturbed and inflamed skin are newly emerging components of the skin immune system. To test the relevance of regulatory B cells (Bregs) in the suppression of cutaneous inflammation, we asked whether impaired migration of these cells into the skin exacerbates skin inflammation. Using a mouse model with a B-cell.specific tamoxifen-inducible deletion of alpha 4 beta 1 integrin, we demonstrate that selective disruption of alpha 4 beta 1-integrin expression in B cells significantly decreases IL-10(+) Bregs in inflamed skin, whereas it does not affect their counterparts in lymphoid tissues. Impaired skin homing and reduced cutaneous accumulation of IL-10(+) Bregs lead to a significant increase in clinical and histopathological parameters of inflammation in both psoriasiform skin inflammation and cutaneous delayed contact hypersensitivity. Thus, our data show a crucial function of skin-homing IL-10(+) Bregs in the suppression of skin inflammation, supporting the notion that Bregs are critical players in the cutaneous environment during inflammatory skin diseases.
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