Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn's disease.
Jia LiAlan J SimmonsCaroline V HawkinsSophie ChironMarisol A Ramirez-SolanoNaila TasneemHarsimran KaurYanwen XuFrank RevettaPaige N VegaShunxing BaoCan CuiRegina N TyreeLarry W RaberAnna N ConnerJennifer M PilatJustin JacobseKara M McNamaraMargaret M AllamanGabriella A RaffaAlain P GobertMohammad AsimJeremy A GoettelYash A ChoksiDawn B BeaulieuRobin L DalalSara N HorstBaldeep S PablaYuankai HuoBennett A LandmanJoseph T RolandElizabeth A ScovilleDavid A SchwartzM Kay WashingtonYu ShyrKeith T WilsonLori A CoburnKen S LauQi LiuPublished in: Nature communications (2024)
Crohn's disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify a distinct epithelial cell type in both terminal ileum and ascending colon (hereon as 'LND') with high expression of LCN2, NOS2, and DUOX2 and genes related to antimicrobial response and immunoregulation. LND cells, confirmed by in-situ RNA and protein imaging, are rare in non-IBD controls but expand in active CD, and actively interact with immune cells and specifically express IBD/CD susceptibility genes, suggesting a possible function in CD immunopathogenesis. Furthermore, we discover early and late LND subpopulations with different origins and developmental potential. A higher ratio of late-to-early LND cells correlates with better response to anti-TNF treatment. Our findings thus suggest a potential pathogenic role for LND cells in both Crohn's ileitis and colitis.
Keyphrases
- induced apoptosis
- cell cycle arrest
- oxidative stress
- poor prognosis
- newly diagnosed
- rheumatoid arthritis
- endoplasmic reticulum stress
- signaling pathway
- gene expression
- ulcerative colitis
- staphylococcus aureus
- risk assessment
- long non coding rna
- pi k akt
- photodynamic therapy
- pulmonary artery
- human health
- nitric oxide
- transcription factor
- dna methylation
- replacement therapy
- drug induced
- nitric oxide synthase
- combination therapy