In tumor immunity, the participation of IL-10eproducing regulatory B cells (Bregs), which play an important role in suppressing immune responses, is unclear. In this study, we demonstrated an increase in B16F10 melanoma growth and a decrease in the proportion of IFN-ge and TNF-aesecreting tumor-infiltrating CD8 þ T cells in B cellespecific PTEN-deficient mice in which Bregs were expanded. The number of tumor-infiltrating Bregs significantly increased in B cellespecific PTEN-deficient mice. More than 50% of tumor-infiltrating B cells consisted of Bregs, predominantly CD19 þ CD5 þ CD43 þ B1a Bregs, in both B cellespecific PTEN-deficient and control mice. Adoptive B1a B cell transfer, which includes >30% of Bregs, increased melanoma growth, whereas non-B1a B cell transfer, which includes <2% of Bregs, exhibited no effect. In addition, adoptive transfer of B1a B cells from wild-type mice, but not IL-10 e/e mice, exacerbated B16F10 melanoma growth. The current study indicates that B1a Bregs negatively regulate anti-melanoma immunity by producing IL-10 and reducing T helper 1 type cytokine production in tumor-infiltrating CD8 þ T cells. Therefore, B1a Bregs can be a potentially novel target for immunotherapy of melanomas.

Aim Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and lung fibrosis. Although SSc has a high mortality risk, an effective treatment for the disease has not been established yet. Mesenchymal stromal/stem cells (MSCs) are multipotential nonhematopoietic progenitor cells that have the ability to regulate immune responses. Adipose‐derived stromal/stem cells (ASCs), one of the types of MSCs, have the advantage of accessibility and potent immunomodulatory effects when compared with other MSCs, such as bone marrow‐derived MSCs. This study aimed to investigate the antifibrotic effect of ASCs in scleroderma mouse models, including bleomycin‐induced scleroderma and sclerodermatous chronic graft‐versus‐host disease (Scl‐cGVHD) models. Method ASCs were intravenously administered to a bleomycin‐induced scleroderma or Scl‐cGVHD model on day 0. We compared the skin and lung fibrosis of scleroderma model mice between the ASC‐treated group and control group. Results Administration of ASCs attenuated the skin and lung fibrosis of bleomycin‐induced scleroderma and Scl‐cGVHD model mice compared to that in the control mice. Immunohistochemical staining showed that ASCs suppressed the infiltration of CD4+, CD8+ T cells and macrophages into the dermis of bleomycin model mice compared to that in control mice. In addition, ASCs attenuated the messenger RNA expression of collagen and fibrogenic cytokines, such as interleukin (IL)‐6 and IL‐13, in the skin of bleomycin model mice. ASCs also reduced the frequency of fibrogenic cytokine‐producing CD4+ T cells and effector B cells in the spleen of bleomycin model mice. Conclusion ASCs could prove to be a potential therapeutic agent for use in patients with SSc.

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.