Background/Purpose:

Psoriasis is a cutaneous disorder characterized by widespread erythematous plaques with adherent scales. Recent studies have revealed that both T helper (Th) 17 and Th1 cells play critical roles in disease development. Histologically, psoriasis is characterized by marked thickening of the epidermis with an inflammatory infiltrate predominantly composed of Th17 and Th1 cells. These infiltrated cells stimulate keratinocytes to produce cytokines, which further amplifies the inflammatory response.

The application of imiquimod occasionally leads to the development of psoriasis in humans. Imiquimod is a potent agonist for Toll-like receptors-7 and -8, and has been used therapeutically in the treatment of a variety of other skin disorders. In mice, the daily topical application of imiquimod induces the appearance of inflamed skin lesions resembling human psoriasis. This experimental method has therefore served as a convenient animal model of the disease.

B cells mediate multiple functions that influence immune and inflammatory responses. Recently, it has been demonstrated that B cells and specific B cell subsets can also negatively regulate immune responses in mice, validating the existence of regulatory B cells. A potent subset of regulatory B cells with a phenotype of CD1d^hiCD5⁺ was recently found to regulate contact hypersensitivity and experimental autoimmune encephalomyelitis in an interleukin (IL)-10-dependent manner. This regulatory B cell subset is called B10 cells to distinguish them from other regulatory B cell subsets that may exist and to identify them as the predominant source of B cell IL-10 production. B10 cell subset is found within the spleen of naïve wild-type mice at 1–2% of the total B cell count, whereas CD19-deficient (CD19^-/-) mice have few, if any, B10 cells. At present, the contribution of regulatory B cells to imiquimod-induced skin inflammation is unclear. Therefore, we examined the importance of regulatory B cells in imiquimod-induced skin inflammation in CD19^-/- and wild-type mice.

Methods:

We treated CD19^-/- and wild-type mice with imiquimod for 6 days and quantitatively evaluated the severity of skin inflammation.

Results:

CD19^-/- mice developed more severe skin inflammation, both clinically and pathologically, than wild-type mice. Splenic B10 cells entered the circulation and migrated to draining lymph nodes during imiquimod-induced skin inflammation, thereby suppressing interferon-g and IL-17 production. Remarkably, the adoptive transfer of spleen B10 cells from wild-type mice ameliorated skin inflammation, whereas either splenic B10 cells from IL-10^-/- mice or non-B10 cells from wild-type mice were without effect.

Conclusion:

IL-10-producing regulatory B10 cells regulated imiquimod-induced skin inflammation. Further studies are needed to determine the precise mechanisms by which regulatory B cells attenuate the severity of psoriasis. Nonetheless, the current results may provide new insights and therapeutic approaches for treating psoriasis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/regulatory-b-cells-suppress-skin-inflammation-in-a-murine-model-of-psoriasis/