IL‐27 Rα⁺ cells promoted allorejection via enhancing STAT1/3/5 phosphorylation

Abstract

Recently, emerging evidence strongly suggested that the activation of interleukin‐27 Receptor α (IL‐27Rα) could modulate different inflammatory diseases. However, whether IL‐27Rα affects allotransplantation rejection is not fully understood. Here, we investigated the role of IL‐27Rα on allorejection both in vivo and in vitro. The skin allotransplantation mice models were established, and the dynamic IL‐27Rα/IL‐27 expression was detected, and IL‐27Rα+ spleen cells adoptive transfer was performed. STAT1/3/5 phosphorylation, proliferation and apoptosis were investigated in mixed lymphocyte reaction (MLR) with recombinant IL‐27 (rIL‐27) stimulation. Finally, IFN‐γ/ IL‐10 in graft/serum from model mice was detected. Results showed higher IL‐27Rα/IL‐27 expression in allografted group compared that syngrafted group on day 10 (top point of allorejection). IL‐27Rα+ spleen cells accelerated allograft rejection in vivo. rIL‐27 significantly promoted proliferation, inhibited apoptosis and increased STAT1/3/5 phosphorylation of alloreactive splenocytes, and these effects of rIL‐27 could be almost totally blocked by JAK/ STAT inhibitor and anti‐IL‐27 p28 Ab. Finally, higher IL‐27Rα+IFN‐γ+ cells and lower IL‐27Rα+IL‐10+ cells within allografts, and high IFN‐γ/low IL‐10 in serum of allorejecting mice were detected. In conclusion, these data suggested that IL‐27Rα+ cells apparently promoted allograft rejection through enhancing alloreactive proliferation, inhibiting apoptosis and up‐regulating IFN‐γ via enhancing STAT pathway. Blocking IL‐27 pathway may favour to prevent allorejection, and IL‐27Rα may be as a high selective molecule for targeting diagnosis and therapy for allotransplantation rejection.

Integrative Analysis From Multicenter Studies Identifies a WGCNA-Derived Cancer-Associated Fibroblast Signature for Ovarian Cancer

“…Immunofluorescence staining was also done by a commercial entity (Servicebio, Wuhan, Hubei, China). According to the company, detailed methods are available in a previous publication (38). Antibody staining order always remains the same, all slices with 4,6-diamidino-2phenylindole (DAPI) (Servicebio, G1012) finally after dyeing.…”

Development and Evaluation of a Novel Radiotracer 125I-rIL-27 to Monitor Allotransplant Rejection by Specifically Targeting IL-27Rα

“…All of these indicated that IL-27/IL-27R was a promising target in the proinflammatory immune response. IL-27R α , the subunit of the IL-27 receptor, which was also expressed in T cells and macrophages, had the highest expression during the acute rejection period in the allograft [44–46]. In our previous study, 125 I-anti-IL-27R α mAb has been found with high specificity towards IL-27R α [19].…”

Identification of the correlations between interleukin-27 (IL-27) and immune-inflammatory imbalance in preterm birth

“…Previous studies have demonstrated that IL-27 promotes allograft rejection by activating the STAT pathway and up-regulating IFN-γ in the skin transplantation mouse model. Based on this, we speculated that increased levels of IL-27 at the maternal-fetal interface might induce PTB by prematurely activating the maternal rejection response to the fetus [ 83 ]. Moreover, as an important part of innate immunity, the complement cascade has recently been considered as a promising direction for PTB study since its activation involved in labor, especially the deposition of complement components C1q and C5b-9 at the maternal-fetal interface.…”