CHBP Induces Stronger Immunosuppressive CD127+ M-MDSC via Erythropoietin Receptor
Urology, Zhongshan Hospital, Fudan University, Shanghai, China
Meeting: 2021 American Transplant Congress
Abstract number: LB 34
Keywords: Immunosuppression, Inflammation, Peptides, Rejection
Topic: Basic Science » Innate Immunity; Chemokines, Cytokines, Complement
Session Information
Session Name: Innate Immunity; Chemokines, Cytokines, Complement
Session Type: Poster Abstract
Session Date & Time: None. Available on demand.
Location: Virtual
*Purpose: Erythropoietin (EPO) is not only an erythropoiesis hormone, but also an immune regulatory cytokine. The receptors of EPO, (EPOR)2 and tissue protective receptor (TPR), mediate EPO’s immune regulation. Our group firstly reported a non-erythropoietic peptide derivant of EPO, cyclic helix B peptide (CHBP), which could inhibit macrophages inflammation and dendritic cells (DCs) maturation. As a kind of innate immune regulatory cell, myeloid-derived suppressor cells (MDSCs) share a common myeloid progenitor with macrophages and DCs. In this study, we investigated the effects on MDSCs differentiation and immunosuppressive function via CHBP induction.
*Methods: MDSC differentiation and function was evaluated with or without CHBP stimulation. To compare the immune regulation difference of M-MDSC with or without CHBP stimulation, murine allo-skin transplant model was established. Signal pathways were detected by western blot, RNA-sequencing and protein array.
*Results: CHBP promoted MDSCs differentiate toward M-MDSCs with enhanced immunosuppressive capability. Infusion of CHBP-induced M-MDSCs significantly prolonged murine skin allograft survival compared to its counterpart without CHBP stimulation. In addition, we found CHBP increased the proportion of CD11b+Ly6G–Ly6Chigh CD127+ M-MDSCs, which exerted stronger immunosuppressive function compared to CD11b+Ly6G–Ly6Chigh CD127– M-MDSCs. In CHBP induced M-MDSCs, we found that EPOR downstream signal proteins Jak2 and STAT3 were upregulated, which had strong relationship with MDSC function. In addition, CHBP upregulated GATA-binding protein 3 (GATA-3) protein translation level, which was an upstream signal of CD127 and regulator of STAT3. These effects of CHBP could be reversed if Epor was deficient.
*Conclusions: Our novel findings identified a new subset of M-MDSCs with better immunosuppressive capability, which was induced by EPOR-mediated Jak2/GATA3/STAT3 pathway. These results are benefit for CHBP clinical translation and MDSC cell therapy in future.
To cite this abstract in AMA style:
Yang C. CHBP Induces Stronger Immunosuppressive CD127+ M-MDSC via Erythropoietin Receptor [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/chbp-induces-stronger-immunosuppressive-cd127-m-mdsc-via-erythropoietin-receptor/. Accessed October 9, 2024.« Back to 2021 American Transplant Congress