Abstract

Psoriasis is an inflammatory cutaneous disease mediated by T-cell dependent immune responses; however, B cells are also considered to play an important role its development. Regulatory B cells (Bregs) regulate immune responses negatively through interleukin-10 (IL-10) production. This study aimed to investigate the role of Bregs in IL-23-mediated psoriasis-like inflammation in mice. Psoriasis-like inflammation was induced in B cell-specific phosphatase and tensin homolog (PTEN)-deficient mice, in which Bregs were significantly expanded, and in their controls, by intradermal injection of 20 μL phosphate-buffered saline (PBS) containing 0.5 μg rmIL-23 into one ear, every other day for 16 days. IL-23-mediated psoriasis-like inflammation was suppressed in B cell-specific PTEN-deficient mice along with decreased ear thickness and epidermal thickness on day 15. Moreover, adoptive transfer of B1 B cells suppressed IL-23-mediated psoriasis-like inflammation. rmIL-23-injected B cell-specific PTEN-deficient mice showed expanded regulatory T cells (Tregs) in the spleen and draining lymph nodes along with increased Bregs. Further, T helper (Th) 17 differentiation in the rmIL-23-injected ear was suppressed in B cell-specific PTEN-deficient mice. Overall, these results indicate that increased Bregs suppress IL-23-mediated psoriasis-like inflammation through Treg expansion and inhibition of Th17 differentiation. Thus, targeting Bregs may be a feasible treatment strategy for psoriasis.

Highlights

  • Psoriasis is an inflammatory cutaneous disease mediated by T-cell dependent immune responses; B cells are considered to play an important role its development

  • These results indicate that increased Bregs suppress IL-23-mediated psoriasis-like inflammation through Treg expansion and inhibition of Th17 differentiation

  • Cd19Cre+/−PtenloxP/loxP mice had less marked hyperkeratosis and acanthosis compared to those in wild type (WT) mice and Cd19Cre+/− mice (Fig. 1A). rmIL-23 injection significantly increased ear thickness and epidermal thickness when compared with phosphate-buffered saline (PBS) control (P < 0.05, P < 0.01 and P < 0.001; Fig. 1B)

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Summary

Introduction

Psoriasis is an inflammatory cutaneous disease mediated by T-cell dependent immune responses; B cells are considered to play an important role its development. T helper (Th) 17 differentiation in the rmIL-23injected ear was suppressed in B cell-specific PTEN-deficient mice Overall, these results indicate that increased Bregs suppress IL-23-mediated psoriasis-like inflammation through Treg expansion and inhibition of Th17 differentiation. Rituximab, a B cell-depleting monoclonal antibody (mAb), has been reported to induce psoriasiform skin lesions in h­ umans[5,6] This finding suggests that B cells have a negative regulatory role in psoriasis development even though it is represented as T cell-mediated autoimmune disorder. In this study, we assessed the role of Bregs in a model of IL-23-mediated psoriasis in B cell-specific PTEN-deficient mice

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