The role of soluble common gamma chain in autoimmune disease

Abstract

The common gamma chain (γc) is the central signaling unit for a number of cytokine receptors collectively known as the γc cytokine receptor family. γc is critical for ligand binding and signaling by γc cytokines. γc cytokine signaling had been thought to be mainly regulated by cytokine-specific receptor α chain expression levels with little or no effect by γc surface levels because γc expression was presumed to remain unchanged during T-cell activation and development. The extent of γc cytokine responses is thought to be regulated by cytokine specific receptor subunits and not by the γc receptor. In contrast to this prevailing view, we have recently reported that γc itself actively regulates γc cytokine responses. Interestingly, γc exerted its regulatory effects not only as a conventional membrane receptor protein but also as a secreted protein whose expression was upregulated upon T-cell stimulation. Here we will review how a soluble form of γc, which is generated by alternative splicing, regulates γc cytokine signaling and plays a role in controlling immune activation related to autoimmune disease.

Soluble γc receptor attenuates anti‐tumor responses of CD8+ T cells in T cell immunotherapy

“…Recently, we identified sγc as an antagonistic regulator for γc cytokines, including IL‐2, IL‐7 and IL‐15, which is important in T cell homeostasis and activation, especially, in the survival, proliferation and effector function of CD8 + T cells . sγc is generated via alternative splicing of γc mRNA, which can then be translated to a truncated form of membrane γc (mγc), and the secreted sγc protein forms a homodimeric structure that binds directly to IL‐2Rβ, another subunit of the cytokine receptors, resulting in the inhibition of IL‐2 and IL‐15 signaling . The proliferation of naïve CD8 + T cells that is responsible to IL‐2 unlike CD4 + T cells were significantly inhibited by sγc .…”

The Role of IL-7 and IL-7R in Cancer Pathophysiology and Immunotherapy

“…sIL-7Rα competes with membrane IL-7R to reduce excessive IL-7 consumption and antagonizes IL-7 signaling, hence enhancing the biological activity of IL-7 when cytokines are restricted [ 33 ]. In addition, sIL-7R directly bind to IL-2Rγ on membrane surface and inhibit IL-7 signaling in IL-2Rγ-positive cells [ 34 ]. Previous studies found that sIL-7Rα aggravate autoimmune diseases [ 33 , 35 , 36 ].…”

Lymphatic Pump Manipulation in Patients with Chronic Obstructive Pulmonary Disease

“…The speed of the lymphatic flow is approximately 125 mL/h in a person at rest but can increase by a factor of 10 during active movements [12][13]. Another passive mechanism that can manage lymphatic flow is oxygen pressure, particularly at low gradients (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40); if the oxygen pressure is higher, the lymphatic flow slows down. Temperature can also influence the speed of the lymphatic flow; the function of the lymphatic system is optimal at temperatures ranging between 32°C and 37°C, and probably acts via extracellular osmotic changes.…”

“…The shared soluble gamma chain (sγc) is used as a mechanotransductional tool by interleukins to communicate with multiple receptor types. [34]. Sγc regulates the functional balance of the immune response; this shared chain influences T lymphatic cells, in particular, a subpopulation of these cells known as T regulatory lymphocytes cells (TREG), and inhibits their inflammatory response [35].…”