Hematopoietic Stem Progenitor Cells Reduce the Proliferation of Tregs via Regulation of IL-12/STAT4 Signaling During Chronic Stress

Authors: Zhang H, Yu S and Yao B*

DOI: 10.23880/aabsc-16000196

Volume 6, Issue 1

Abstract

Physical or psychological chronic stress mediates the impaired immune response by inducing the proliferation of regulatory T cells (Tregs). Our recent studies showed that hematopoietic stem progenitor cells (HSPCs) significantly modulated the immune system. HSPCs prevented stress-induced lymphocyte apoptosis, exerting a protective effect in chronic stress-induced immune responses. Thus, whether HSPCs could prevent the proliferation of Tregs in conditions of chronic stress was assessed in the present study. Injection of HSPCs inhibited the proliferation of Tregs and reduced the expression of inhibitory molecules of Tregs under conditions of chronic stress. Additionally, the protective effects of HSPCs were shown to be dependent on IL12. IL-12/STAT4 signaling in the modulation of proliferation of Tregs induced by chronic stress. When HSPC injection was co-administered with an IL-12 neutralizing antibody or selective STAT4 inhibitor in chronic stressed mice, the protective effects of HSPCs were abrogated. Injection of HSPCs increased IL-12 production by splenocytes in chronic stressed mice. These results suggest that HSPCs inhibit the proliferation of Tregs and this is dependent on IL-12 production to protect the impaired immune response.

Keywords: Tregs; FOXP3; IL-12; Chronic Stress; Immune Impairment

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