M2‐like macrophages polarized by Foxp3⁻Treg‐of‐B cells ameliorate imiquimod‐induced psoriasis

Abstract

Our group have demonstrated that splenic B cells contributed to the CD4+CD25− naive T cells conversion into CD4+CD25+Foxp3− regulatory T cells without adding appended cytokines, named Treg‐of‐B cells which were potent suppressors of adaptive immunity. We like to investigate whether Treg‐of‐B cells could promote alternatively activated macrophage (M2 macrophages) polarization and alleviate inflammatory disease, psoriasis. In this study, we co‐cultured the bone marrow‐derived macrophages (BMDMs) with Treg‐of‐B cells under LPS/IFN‐γ stimulation and analyzed the M2‐associated gene and protein using qPCR, western blotting, and immunofluorescence staining. We also examined the therapeutic effect of Treg‐of‐B cell‐induced M2 macrophage for skin inflammation using imiquimod (IMQ)‐induced psoriatic mouse model. Our results showed that BMDMs co‐cultured with Treg‐of‐B cells upregulated typical M2‐associated molecules, including Arg‐1, IL‐10, Pdcd1lg2, MGL‐1, IL‐4, YM1/2 and CD206. In an inflammatory environment, TNF‐α and IL‐6 production by macrophages co‐cultured with Treg‐of‐B cells was decreased significantly. The molecular mechanism revealed that Treg‐of‐B cells promoted M2 macrophage polarization via STAT6 activation in a cell contact‐dependent manner. Moreover, the treatment with Treg‐of‐B cell‐induced M2 macrophages attenuated the clinical manifestations of psoriasis, such as scaling, erythema and thickening in the IMQ‐induced psoriatic mouse model. T cell activation in draining lymph nodes was decreased in the Treg‐of‐B cell‐induced M2 macrophage group after IMQ application. In conclusion, our findings suggested that Foxp3− Treg‐of‐B cells could induce alternatively activated M2 macrophages through STAT6 activation, providing a cell‐based therapeutic strategy for psoriasis.

Macrophage Functions in Psoriasis: Lessons from Mouse Models

“…This can likely be achieved by modulating STAT-dependent pathways under regulatory T (Treg) cell activity. Accordingly, forkhead box p3 (Foxp3)-negative Tregof-B cells were recently shown to promote M2 macrophage polarization through STAT6 activation in an imiquimod-induced psoriasis model [102]. Moreover, the therapeutic use of non-coding ribonucleic acids (RNAs) and EVs is currently attracting research attention.…”

The immunological understanding on germinal center B cells in psoriasis

“…At present, psoriasis is a unique autoimmune disease as it has no definite pathogenesis, though, the overall hypothesized pathogenesis accentuates how T cells play a massive role in developing psoriasis (Wang et al, 2023). The knowledge of how B cells can interfere with psoriasis development with its functionality in a similar role is regarded as newly discovered (Alrefai et al, 2016; Huang et al, 2023). However, it is still required to have an in‐depth immunological understanding before assessing any targeting cytokines and B cells.…”