CD4⁺ T Cell Fate in Glomerulonephritis: A Tale of Th1, Th17, and Novel Treg Subtypes

Figure 3

The immune system gives rise to different CD4⁺ T cell lineages. Among these are Th effector cells (Teff), which can differentiate into Th1 and Th17 cells during inflammation. Furthermore, there are conventional RORγt⁻Foxp3⁺ Tregs (cTreg), which have the potential to develop into specialized Treg1 and Treg17 cells. Finally, a third and hitherto unrecognized independent Treg cell lineage exists, which is characterized by simultaneous expression of RORγt and Foxp3. During inflammation, for example, glomerulonephritis, they rapidly expand by proliferation and start to produce great amounts of pro- and anti-inflammatory cytokines. Subsequently, their population retracts by downregulating both transcription factors, RORγt and Foxp3, to become ex-RORγt⁺ Tregs. The functional properties of these ex-RORγt⁺ Tregs remain elusive to date.