Figure 2. Lateral association of CD69 with transmembrane receptors. A) CD69 is associated with S1P1 on T and B cells which leads to downmodulation and degradation of S1P1, and impairs cell migration to S1P-dependent chemotaxis. B) CD69 interacts with the amino acid transporter SLC7A5-SLC3A2, also known as LAT1-CD98, stabilizing the expression of SLC7A5 on the T cell membrane. This interaction favors the amino acid uptake, increasing leucine (Leu) transport that activates mTORC and promotes Th17 cell differentiation. HIF-1α is also stimulated by mTORC and mediates Th17 differentiation. CD69 increases the uptake of tryptophan (Trp) and the Trp-derived metabolite FICZ, which is an AHR agonist. AHR activation induces the transcription of IL-22 and CD39 mRNA. AHR modulates HIF-1α levels and vice versa, which can also impact in the Th17 cell differentiation program. This figure was created with BioRender.com.