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. 2021 Jun 4;12:684642. doi: 10.3389/fimmu.2021.684642

Figure 3.

Figure 3

Common gamma chain cytokine signaling and synthetic receptors. (A) Common gamma chain cytokine receptors IL-2/15R, IL-7R, and IL-9R signal primarily through STAT5 while IL-21R signals primarily through STAT3. IL-4R signals through STAT6 to induce Th2 polarization. These receptors also activate PI3K and all except IL-7R activate MAPK pathways. (B) Constitutive active variants of IL-7R can provide constant STAT5 activation. C7R is formed from homodimerization of IL-7Rα chain mutants through a disulfide bridge in the transmembrane domain. A constitutively active IL-7R provides constant STAT5 and PI3K signaling by expression of IL-7 tethered to IL-7Rα. Switching the IL-7Rα intracellular domain with IL-2Rβ provides constant STAT5, PI3K, and MAPK signaling. (C) Switch receptors bind an immunosuppressive cytokine, such as IL-4, and convert it into a stimulatory signal. These receptors are composed of the IL-4Rα extracellular domain (IL-4Rex) fused to the IL-7Rα, IL-2Rβ, or IL-21R intracellular domain (IL-7Rin, IL-2Rin, or IL-21Rin).