The death and resurrection of IRGM – the “Jesus gene”
Autophagy: Eat thyself, Heal thyself.
The IRGM gene, once was lost but now is found, regulates autophagy. Certain dysfunctional polymorphisms of this gene are linked to susceptibility to Crohn’s Disease, Tuberculosis, SLE and Gastric Cancer.
Understandably, autophagy failure can lead to failure in intracellular clearance of TB, and impair cancer surveillance.
IRGM also provides negative feedback to IFN-γ, the over-production of which is pathological in SLE, and overdrives haemopoietic stem cells to exhaustion and hence explains the cytopaenias often encountered in chronic inflammation. Can certain autoimmune non-genetic forms of Myelodysplastic Syndrome result from such mechanisms?
Autophagy failure can drive T-cell proliferation, bridging aberrant innate immunity with adaptive immune disorder. Can some forms of autoinflammatory-autoimmune diseases like SLE and Crohn’s have defective IRGM resulting in autophagy failure, excessive IFN-γ production and aberrant T-cell response?
Certain viruses are able to inhibit IRGM function to improve its own survivability within infected cells. Certain viral infections, in defective IRGM individuals, may then ostensibly trigger autoimmunity. Can H pylori act similarly to cause gastric cancer?