SOCS3 and IL7Ra regulation
Suppressor of Cytokine Signaling (SOCS) 3 is a major regulator of cytokine signaling, with known implications in inhibition of signal transduction and cytokine receptor degradation by interfering with the JAK/STAT pathway. In addition, an inhibitory effect of SOCS3 has also been described upon T-cell activation. By binding the TCR co-receptor CD28, SOCS3 can downregulate the PI3K/Akt pathway leading to decreased levels of transcription factors implicated on T-cell homeostasis and memory generation.
IL7Ra is central in sensing IL7 and generating protective T-cell memory. Interestingly, both IL7 and TCR stimulation lead to a reduction on IL7Ra expression, followed by a re-expression of the receptor at later time points.
In our lab, we aim to characterize the mechanisms implicated in the regulation of IL7Ra expression upon TCR activation by lentiviral modulation of SOCS3 in T cells and the potential impact on T-cell homeostasis and memory formation.