Stability and Maintenance of Foxp3+ Treg Cells in Non-lymphoid Microenvironments

Abstract

Foxp3+ Treg cells are indispensable for maintaining self-tolerance in secondary lymphoid organs (SLOs). However, Treg cells are also recruited to non-lymphoid tissues (NLTs) during inflammation. Recent advances in the understanding of Treg cell biology provided us with molecular mechanisms—both transcriptional and epigenetic—that enable Treg cells to retain their identity in an inflammatory milieu that is per se hostile to sustained expression of high levels of Foxp3. While Treg cells are recruited to sites of inflammation in order to resolve inflammation and re-establish appropriate organ function, it is increasingly recognized that a series of inflammatory (but also non-inflammatory) perturbations of organ function lead to the constitution of relatively long lived populations of Treg cells in NLTs. NLT Treg cells are heterogeneous according to their respective site of residence and it will be an important goal of future investigations to determine how these NLT Treg cells are maintained, e.g., what the role of antigen recognition by NLT Treg cells is and which growth factors are responsible for their self-renewal in the relative deficiency of IL-2. Finally, it is an open question what functions NLT Treg cells have besides their role in maintaining immunologic tolerance. In this review, we will highlight and summarize major ideas on the biology of NLT Treg cells (in the central nervous system but also at other peripheral sites) during inflammation and in steady state.

Evaluation of inflammation and follicle depletion during ovarian ageing in mice

“…Another subset of T cells, termed regulatory T cells (Treg), are also recruited to sites of inflammation in peripheral tissues in order to resolve inflammation and restore the correct organ function 64 . Recently, Dong et al suggested some natural regulation of ovarian integrity by Tregs, since depletion of Treg cells by neonatal thymectomy results in autoimmune ovarian disease 65 .…”

Identification of a Prognostic Immune Signature for Esophageal Squamous Cell Carcinoma to Predict Survival and Inflammatory Landscapes

“…The previous research proved that Tregs could promote progression of ESCC, whereas both Tregs and fibroblasts were relevant to unfavorable survival in patients with ESCC (Fu et al, 2011;Nabeki et al, 2015;Yue et al, 2020). Meanwhile, α-SMA and Foxp3 are specific biomarkers of fibroblasts and Treg cells (Korn and Muschaweckh, 2019;Zhan et al, 2019). To confirm our analytical results, we first selected two representative tumor samples from the high-and low-risk groups and stained α-SMA and Foxp3 in the two tumor sample slices using the immunofluorescent assay method.…”

Heterogeneity of T Cells in Atherosclerosis Defined by Single-Cell RNA-Sequencing and Cytometry by Time of Flight

“… 105 In addition, it has been established that other proinflammatory cytokines or lipopolysaccharide promote Foxp3 degradation. 106 Likewise, several signaling pathways such as these involving the TF NFκB (nuclear factor κ-light-chain-enhancer), IRF (interferon regulatory factor)-4, Runx (Runt-related transcription factor), FoxP (Forkhead box protein P)-1, the nuclear protein DBC (deleted in breast cancer)-1, and serine/threonine-Pak (protein kinase)-2 (reviewed in study by Korn and Muschaweckh 107 ) as well as self-peptide induced TCR-signaling 108 have been linked to the plasticity of T regs . Altogether, these findings demonstrate a strong association of inflammation and T reg -instability, which sparks the yet unproven hypothesis that the multitude of factors that initiate and maintain atherosclerosis, such as local and systemic inflammation, LDL (low-density lipoprotein), vascular integrity and injury, immune cell accumulation, and antigen-recognition by T regs , favor a stage- and context-specific conversion of an initial protective into a pathogenic immune response (Figure 2 ).…”