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Arginine Modifying Enzymes: Regulators of Immune Function Kerri A. Mowen, Assistant Professor, The Scripps Research Institute
- 1. 1/13/2010 Arginine Modifying Enzymes: Regulators of Immune Function or NIP45 Controls the Magnitude of a Type 2 Immune Response 1. Importance of the transcriptional cofactor NIP45 in the Type 2 immune response. 2. Negative regulation of NIP45 by an arginine deiminase T Helper Cell Subsets Th1 Th2 Th17 SUBSET: CYTOKINE: IFNγ, IL‐2 IL‐4, IL‐13, IL‐17, IL‐17F, TNFα TNF IL‐5, IL‐10 IL 5 IL 10 IL‐22, IL‐21 IL 22 IL 21 Intracellular Extracellular Bacterial & L. major T. spiralis Fungal PATHOGEN: L. monocytogenes N. brasiliensis Infections M. tuberculosis PATHOLOGY: Autoimmunity Asthma Autoimmunity Allergy 1
- 2. 1/13/2010 CD4 TCR Calcineurin IL-2, IL-4, IL- IL 2 IL 4 IL 13, IL-5, & IFNγ NFAT NFAT NIP45: NFAT-Interacting Protein 45 •isolated via interaction with the RHD of NFAT NFATc2 • predominantly nuclear c-Maf • high expression in spleen & NFATc2 thymus c-Maf •no obvious functional domains NIP45 0 100 200 • NIP45 in conjunction with NFAT IL-4 Concentration & c-Maf transactivates the IL-4 (pg/ml) promoter Science 1996 v274:1903 Impaired T helper cytokine production in the absence of NIP45 2
- 3. 1/13/2010 T. spiralis expulsion requires T cells and Mast cells Reduced serum IL-4 levels in T. spiralis infected NIP45 KO mice Elevated worm burden in NIP45 KO mice 3
- 4. 1/13/2010 NIP45-/- MLN T helper cells are impaired in Type 2 cytokine expression during infection with T. spiralis NIP45 amino terminus is methylated by PRMT1 Molecular Cell 15:559 NIP45 N-terminus mediates PRMT1 activity PRMT1 NIP45 NFAT 4
- 5. ATTENTION! The entire presentation is available to registered attendees only! To view the rest of this exciting presentation and many more! Please Register for the 8th Annual Cytokines & Inflammation Conference at www.gtcbio.com If you are already registered, please contact GTCbio for the full version.