fig1

Figure 1. (A) Treg and Th17 lymphocyte differentiation. Treg and Th17 lymphocytes share a common signaling pathway by TGF-β. The cytokine milieu plays a key part in the differentiation to these different subsets. Upon exposition to IL-6 or IL-23, naïve CD4⁺ lymphocytes differentiate into Th17 cells. The main cytokines produced by Th17 cells are IL-17A, IL-17F, IL-21, and IL-22. On the other hand, in the absence of proinflammatory cytokines, TGF-β alone or together with IL-2 drives the differentiation to Tregs. Tregs produce anti-inflammatory cytokines such as IL-10 and TGF-β. (B) In homeostasis, there is a balance between Treg and Th17 populations. The main function of Th17 cells is host defense against extracellular pathogens, whereas Tregs’ main functions are to maintain peripheral immune tolerance and modulate immune responses. (C) During inflammaging, the Treg/Th17 balance is disrupted. Exacerbated Th17 responses lead to autoimmunity and inflammatory diseases and Tregs are described to be less tolerogenic. TGF-β: Transforming growth factor-beta; RORγt: retinoic acid receptor-related orphan receptor gamma-t; Foxp3: forkhead box p3; DCs: dendritic cells; CTLA-4: cytotoxic T lymphocyte antigen 4; LAG-3: lymphocyte-activation gene 3.