The role of Treg subtypes in glomerulonephritis
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REVIEW
The role of Treg subtypes in glomerulonephritis G. R. Herrnstadt1 · O. M. Steinmetz1 Received: 1 September 2020 / Accepted: 18 November 2020 © The Author(s) 2020
Abstract While Th1 and Th17 T effector cells are pathogenic drivers of glomerulonephritis (GN), regulatory T cells (Tregs) potently protect from renal tissue injury. Recently, it has become evident that different Treg subtypes exist. Among these are lineage specific Treg1 and Treg17 cells, which are specialized to down regulate either Th1 or Th17 T effector cell responses. Interestingly, programming of specialized Tregs and the corresponding T helper effector cells depend on the same lineage specific master transcription factors Tbet (Th1/Treg1) and STAT3 (Th17/Treg17). Furthermore, early control of T effector cell priming in secondary lymphoid organs by specialized Tregs was described. One central mechanism of T effector cell control by the corresponding Treg subtype seems to be expression of the same chemokine receptor repertoire, which facilitates their co-localization. More recently, another intriguing Treg subset was identified, which expresses Foxp3 together with the Th17 characteristic transcription factor RORγt. While these F oxp3+RORγt+ Tregs were shown to be highly immunosuppressive, studies in GN also identified pro-inflammatory potential via secretion of IL-17. Many questions regarding this unusual Treg subset remain, including their origin, stability, and mechanisms of action. Further characterization of the renal Treg landscape during GN will help to identify novel immunosuppressive mechanisms and develop successful Treg-directed therapies. In this review, we summarize the currently available data about specialized Treg subsets and discuss their role in GN.
Introduction CD4+ T effector cells (Teff) and in particular the T helper 1 (Th1) and 17 (Th17) lineages are crucial pathogenic mediators of crescentic glomerulonephritis (GN) (Krebs et al. 2017; Kurts et al. 2013; Phoon et al. 2008; Steinmetz et al. 2011). Interestingly, Th17 cells, characterized by activation of the master transcription factor RORγt and the production of IL-17A+F, showed high abundancy in nephritic kidneys of patients with ANCA-associated vasculitis and significantly aggravated crescentic nephritis in experimental models (Krebs et al. 2016; Paust et al. 2009; Steinmetz et al. 2011). This indicates their central pathogenic importance and highlights their therapeutic potential. Regulatory T cells (Treg) in contrast have the capacity to counter-regulate over-shooting immune responses, which has been shown to protect from a large number of autoimmune diseases including GN (Kurts et al. 2013; Steinmetz et al. 2010; Vignali * O. M. Steinmetz [email protected] 1
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52., 20246 Hamburg, Germany
et al. 2008). As a consequence, Tregs became promising therapeutic targets (Bluestone and Tang 2018; Raffin et al. 2019). Human studies of ANCA-associated vasculitis, Systemic Lupus Er
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