fig2

Figure 2. Signaling pathways of Treg and Th17 lymphocyte differentiation. Upon interaction with IL-6, the cytoplasmic tail of IL-6R associates with Jak1 and Jak2, triggering phosphorylation of Stat3 and its translocation to the nucleus, where it can activate the transcription factor RORγt and induce Th17 cell differentiation. On the other hand, Treg differentiation is triggered by IL-2R and CD69 in a non-redundant way. After interaction with IL-2 or CD69 ligands (OxLDL, alarmins S100A8/A9 or Gal-1), Jak3 is recruited in the cytoplasmatic tails of IL-2R and CD69, respectively. Then, STAT5 is phosphorylated, dimerized, and translocated to the nucleus, where it promotes the expression of Foxp3. IL2R/CD69-dependent activation of STAT5 inhibits the Th17 cell differentiation pathway by preventing SSTAT3 translocation to the nucleus and suppressing STAT3-mediated RORγt activation through the induction of Foxp3 expression. STAT: Signal transducer and activator of transcription; Jak: Janus Kinase; RORγt: retinoic acid receptor-related orphan receptor gamma-t; OxLDL: oxidized low-density lipoprotein; Foxp3: forkhead box p3.