Mechanisms underlying immunosuppression by regulatory cells

Abstract

Regulatory cells, such as regulatory T cells (Tregs), regulatory B cells (Bregs), and myeloid-derived suppressor cells (MDSCs), play a crucial role in preserving immune tolerance and controlling immune responses during infections to prevent excessive immune activation. However, pathogens have developed strategies to hijack these regulatory cells to decrease the overall effectiveness of the immune response and persist within the host. Consequently, therapeutic targeting of these immunosuppressive mechanisms during infection can reinvigorate the immune response and improve the infection outcome. The suppressive mechanisms of regulatory cells are not only numerous but also redundant, reflecting the complexity of the regulatory network in modulating the immune responses. The context of the immune response, such as the type of pathogen or tissue involved, further influences the regulatory mechanisms involved. Examples of these immunosuppressive mechanisms include the production of inhibitory cytokines such as interleukin 10 (IL-10) and transforming growth factor beta (TGF-β) that inhibit the production of pro-inflammatory cytokines and dampen the activation and proliferation of effector T cells. In addition, regulatory cells utilize inhibitory receptors like cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) to engage with their respective effector cells, thereby suppressing their function. An alternative approach involves the modulation of metabolic reprogramming in effector immune cells to limit their activation and proliferation. In this review, we provide an overview of the major mechanisms mediating the immunosuppressive effect of the different regulatory cell subsets in the context of infection.

The association between the neutrophil-to-lymphocyte ratio and type 2 diabetes mellitus: a cross-sectional study

“…Studies have indicated that IL-17 can stimulate the production of TNF-α and is implicated in the development of IR [ 36 ]. Regulatory T (Treg) cells constitute a minor subset of T lymphocytes known for their pivotal role in suppressing inflammatory responses [ 37 ]. During the progression of diabetes, Treg cells can inhibit Th1 and Th17 cell responses through the regulation of the microenvironment and alteration of surface receptor expression, consequently ameliorating IR [ 38 ].…”