IL-Y, a synthetic member of IL-12 cytokine family, was found to exert potent immunosuppressive effects by inhibiting the differentiation and activation of Th1 and Th17 cells. However, the role of IL-Y in the development of chronic graft-versus-host disease (cGVHD) remains unknown. Here, using murine models of scleroderma-like and lupus-like cGVHD, we examined the function of IL-Y in the pathogenesis of cGVHD by hydrodynamically injecting minicircle-IL-Y expressing plasmids (MC IL-Y). In contrast with the reported immune suppressive function of IL-Y, administration of MC IL-Y enhanced cGVHD severity reflected by deteriorated multi-organ pathologic damages. In lupus-like cGVHD model, urine protein and the serum anti-dsDNA antibody (IgG) were significantly upregulated by IL-Y treatment. Further study demonstrated that IL-Y impacts both donor T and B cell response. In T cells, IL-Y inhibited the generation of CD4+Foxp3+ regulator T (Treg) cells during the development of cGVHD. IL-Y may also increase the infiltration of pathogenic TNF-α producing CD4+ and CD8+ T cells through IL-27Rα in recipient spleens, as this effect was diminished in IL-27Rα deficient T cells. Moreover, IL-Y enhanced the differentiation of ICOS+ T follicular helper (Tfh) cells. In B cells, the percentage of germinal center (GC) B cells in recipient spleens was significantly upregulated by MC IL-Y plasmid administration. The levels of co-stimulatory molecules, MHC-II and CD86, on B cells were also enhanced by IL-Y expression. Taken together, our data indicated that IL-Y promoted the process of cGVHD by activating pathogenic T and B cells.
Copyright © 2020 Wan, Jin, Hu, Lv, Lei, Liu, Song, Zhu, Gong, Xu, Du, Xu, Liu, Wu and Liu.

Bone morphogenic proteins (BMPs) are members of the transforming growth factor β (TGF-β) cytokine family promoting differentiation, homeostasis, and self-renewal of multiple tissues. We show that signaling through the bone morphogenic protein receptor 1α (BMPR1α) sustains expression of FOXP3 in Treg cells in peripheral lymphoid tissues. BMPR1α signaling promotes molecular circuits supporting acquisition and preservation of Treg cell phenotype and inhibiting differentiation of pro-inflammatory effector Th1/Th17 CD4+ T cell. Mechanistically, increased expression of KDM6B (JMJD3) histone demethylase, an antagonist of the polycomb repressive complex 2, underlies lineage-specific changes of T cell phenotypes associated with abrogation of BMPR1α signaling. These results reveal that BMPs are immunoregulatory cytokines mediating maturation and stability of peripheral FOXP3+ regulatory T cells (Treg cells) and controlling generation of iTreg cells. Thus, we establish that BMPs, a large cytokine family, are an essential link between stromal tissues and the adaptive immune system involved in sustaining tissue homeostasis by promoting immunological tolerance.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Interleukin (IL)-23 is one of the newly identified inflammatory cytokines, and inflammation is also known to be related to the development of gastric cancer (GC). The role of IL-23 in gastric cancer, however, is largely unknown. In the present study, we investigated the expression and possible role of IL-23A in human GC.
The expression of IL-23A and IL-17A in human GC tissues was determined by immunohistochemistry, and the relationship between IL-23A expression and clinical characteristics of GC was investigated. The serum concentration of IL-23A and IL-17A was also tested by ELISA. The source and role of IL-23A in GC were studied in vitro by Flowcytometry, MTS (Owen's reagent) assay and Western blot.
IL-23A, IL-23 receptor (IL-23R) and IL-17A were all overexpressed in human GC tissues, and the level of IL-23A was well correlated with IL-17A in GC tissues as well as in patient's serum. Macrophages and GC cells were the main source of IL-23A secretion upon stimulation of H. pylori lysate. Furthermore, we found that IL-23A promoted proliferation of GC cell lines via IL-17A/IL-17 receptor antagonist (IL-17RA) /nuclear factor-κB (NF-κB) signaling.
The high expression of IL-23A is associated with GC. IL-23A can promoted GC cells growth by inducing the secretion of IL-17A in tumor microenvironment. Our results suggest that the serum concentration of IL-23A is a good biomarker of poor clinical prognosis in GC patients.