The amino acid sensor GCN2 inhibits inflammatory responses to apoptotic cells promoting tolerance and suppressing systemic autoimmunity

• DOI: 10.1073/pnas.1504276112
• Publication Date: 2015-08-11T02:30:34Z
• Authors: Buvana Ravishankar; Haiyun Liu; Rahul Shinde; Kapil Chaudhary; Wei Xiao; Jillian Bradley; Marianne Koritzinsky; Michael P. Madaio; Tracy L. McGaha
• Keywords: Inflammation; Mice, Knockout; 0301 basic medicine; Macrophages; Apoptosis; Autoimmunity; Protein Serine-Threonine Kinases; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Gene Expression Regulation; Piperidines; Immune Tolerance; Animals; Cytokines; Indoleamine-Pyrrole 2,3,-Dioxygenase; Lupus Erythematosus, Systemic; Myeloid Cells; Amino Acids; Cells, Cultured; Quinazolinones

Significance Metabolic stress potently modifies immunity. Recently our laboratory identified the kinase GCN2 as a key modulator of macrophage responses to toll-like receptor ligands; however, role myeloid signals in sterile inflammation and homeostatic tolerance is not known. In this study, we tested requirement for apoptotic cells prevention autoimmunity model lupus. Our results show that critical effector cell-driven required regulatory cytokine production inflammatory Moreover, data indicate targeting an effective approach preventing autoimmunity, providing rationale developing tools manipulate function immune disease.