New Frontiers in Genetics, Gut Microbiota, and Immunity: A Rosetta Stone for the Pathogenesis of Inflammatory Bowel Disease

Table 1

Selected candidate genes in the 38 newly associated IBD susceptibility loci.

Gene name	Aliases	GO annotations	Previous associated diseases	Novel biological significance in IBD	References
PTGS2	Prostaglandin-endoperoxide synthase 2	Protein homodimerization activity and lipid binding	Colorectal adenoma and peptic ulcer disease	Inhibiting T cell activation and promoting regulatory T cell development	[38–40]
LY75	Lymphocyte antigen 75	Receptor activity and carbohydrate binding	Hodgkin lymphoma and lipid pneumonia	Participating in T cell function and homeostasis	[41, 42]
CD28	CD28 molecule	Identical protein binding and SH3/SH2 adaptor activity	Sezary’s disease and mycosis fungoides	A key costimulatory molecule in T cell activation and preventing aberrant immunological responses to intestinal antigens	[43, 44]
CCL20	C-C motif chemokine ligand 20	Cytokine activity and chemokine activity	Rheumatoid arthritis and bejel	Regulating the migration of T cells (especially regulatory T cells) and dendritic cells to the gut	[45–47]
NFKBIZ	NFKB inhibitor zeta	Transcription cofactor activity	Myxoid liposarcoma and brain glioblastoma multiforme	Activate natural killer cell, recruiting monocyte, and regulating Th17 development with ROR nuclear receptors	[48, 49]
OSMR	Oncostatin M receptor	Growth factor binding and oncostatin M receptor activity	Amyloidosis, primary localized cutaneous, 1 and amyloidosis	Promoting intestinal epithelial cell proliferation and wound healing	[50]
AHR	Aryl hydrocarbon receptor	Transcription factor activity, sequence-specific DNA binding and protein heterodimerization activity	Eosinophilic fasciitis and seborrheic dermatitis	Maintaining intraepithelial lymphocyte homeostasis and controlling intestinal microbial load and composition	[51, 52]
PTK2B	Protein tyrosine kinase 2 beta	Transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity	Transient cerebral ischemia and osteoporosis	Monocyte migration and neutrophil degranulation	[53]
NFATC1	Nuclear factor of activated T cells 1	Transcription factor activity, sequence-specific DNA binding, and transcription regulatory region DNA binding	Bone epithelioid hemangioma and ventricular septal defect	Supporting lymphocyte proliferation and inhibiting activation-induced cell death	[54, 55]