Cytokine receptors on T and NK cells

Cytokine receptors on T and natural killer (NK) cells are a diverse group of cell-surface proteins that mediate the effects of cytokines, which are critical signaling molecules in the immune system. These receptors, such as the interleukin-2 (IL-2) receptor and interleukin-15 (IL-15) receptor, typically consist of multiple subunits that, upon ligand binding, activate intracellular signaling pathways like the JAK-STAT pathway to regulate cell growth, differentiation, and effector functions (Waldmann, 2018, Nature Reviews Immunology). In oncology, these receptors are targeted to enhance the anti-tumor activity of T and NK cells, while in autoimmune diseases, they are targeted to inhibit pathological immune activation (Leonard & Lin, 2000, Nature Reviews Immunology). Therapeutic strategies include the use of recombinant cytokines, monoclonal antibodies, and chimeric antigen receptor (CAR) modifications to modulate these signaling axes (Villarino et al., 2017, Nature Immunology). However, manipulating these receptors carries risks such as cytokine release syndrome or severe systemic toxicity due to their broad expression and potent biological effects (Kroschinsky et al., 2017, Critical Care). Understanding the specific expression patterns and signaling thresholds of these receptors is essential for developing precise immunotherapies that maximize efficacy while minimizing off-target effects (O'Shea et al., 2013, Nature Reviews Drug Discovery). These receptors often share common subunits, such as the common gamma chain (CD132), which complicates the selective targeting of individual cytokine pathways (Liao et al., 2013, Immunity). Recent advances in protein engineering have led to the development of biased agonists designed to trigger specific receptor conformations for more favorable therapeutic outcomes (Silva et al., 2019, Nature).

Other names

Interleukin receptorsInterferon receptorsCommon gamma chain receptorsLymphocyte cytokine receptors

Drugs targeting these receptors function as agonists to promote the expansion and activation of T and NK cells for cancer treatment, or as antagonists/monoclonal antibodies to block cytokine signaling in the context of autoimmune disorders and transplant rejection (Waldmann, 2018, Nature Reviews Immunology).