The role of Treg subtypes in glomerulonephritis

Abstract

AbstractWhile 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 Foxp3+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.