Structural Basis for Signaling Through Shared Common γ Chain Cytokines

IL-2 can signal via chemokine receptors to promote regulatory T cells’ suppressive function

“…Because non-canonical IL-2 signaling is promoted by monoclonal antibodies or components of the extracellular matrix, we suggest the acronym M-directed alternative cytokine signaling (MACS) for convenience ( Figure 6D ). Notably, IL-2 is a member of a family of 6 cytokines that have distinct α subunits and that signal through a common γ c subunit, 55 raising the possibility that MACS involving other cytokines might also engage unexpected signaling receptors. Thus, we show that HS, antibodies against IL-2, or anti-CD25 can direct IL-2 to CCR7 to trigger a MACS pathway that enhances Treg function.…”

Case Report: A Novel IL2RG Frame-Restoring Rescue Mutation Mimics Early T Cell Engraftment Following Haploidentical Hematopoietic Stem Cell Transplantation in a Patient With X-SCID

“…X-linked severe combined immunodeficiency (X-SCID) is caused by defects in the gene encoding for the common gamma chain (interleukin 2 receptor gamma) and represents the most common form of SCID (3)(4)(5). The common cytokine receptor g-chain is shared by the receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 and IL-21 and abnormalities in cytokine signaling reflect the X-SCID immunophenotype (6,7). These cytokines are essential in early T cell differentiation as well as NK cell development and B cell function.…”