Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn's disease

被引：10

作者：

Li, Jia ^{[1
,2
]}

Simmons, Alan J. ^{[3
,4
]}

Hawkins, Caroline V. ^{[5
]}

Chiron, Sophie ^{[5
]}

Ramirez-Solano, Marisol A. ^{[1
,2
]}

Tasneem, Naila ^{[3
,4
]}

Kaur, Harsimran ^{[3
,6
]}

Xu, Yanwen ^{[3
,4
]}

Revetta, Frank ^{[7
]}

Vega, Paige N. ^{[3
,4
]}

Bao, Shunxing ^{[8
]}

Cui, Can ^{[9
]}

Tyree, Regina N. ^{[5
]}

Raber, Larry W. ^{[5
]}

Conner, Anna N. ^{[5
]}

Pilat, Jennifer M. ^{[5
]}

Jacobse, Justin ^{[5
]}

Mcnamara, Kara M. ^{[5
,10
]}

Allaman, Margaret M. ^{[5
]}

Raffa, Gabriella A. ^{[5
]}

Gobert, Alain P. ^{[5
,10
,11
]}

Asim, Mohammad ^{[5
]}

Goettel, Jeremy A. ^{[5
,7
,10
,11
]}

Choksi, Yash A. ^{[5
,10
,11
,12
]}

Beaulieu, Dawn B. ^{[5
]}

Dalal, Robin L. ^{[5
]}

Horst, Sara N. ^{[5
]}

Pabla, Baldeep S. ^{[5
]}

Huo, Yuankai ^{[8
,9
]}

Landman, Bennett A. ^{[8
,9
]}

Roland, Joseph T. ^{[3
,13
]}

Scoville, Elizabeth A. ^{[5
,11
]}

Schwartz, David A. ^{[5
]}

Washington, M. Kay ^{[6
,11
]}

Shyr, Yu ^{[1
,2
]}

Wilson, Keith T. ^{[5
,7
,10
,11
,12
]}

Coburn, Lori A. ^{[5
,10
,11
,12
]}

Lau, Ken S. ^{[1
,3
,4
,6
,11
,13
]}

Liu, Qi ^{[1
,2
]}

机构：

[1] Vanderbilt Univ, Med Ctr, Ctr Quantitat Sci, Nashville, TN 37235 USA

[2] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN 37235 USA

[3] Vanderbilt Univ, Med Ctr, Epithelial Biol Ctr, Nashville, TN 37235 USA

[4] Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37235 USA

[5] Vanderbilt Univ, Med Ctr, Dept Med, Div Gastroenterol Hepatol & Nutr, Nashville, TN 37235 USA

[6] Vanderbilt Univ, Sch Med, Program Chem & Phys Biol, Nashville, TN 37235 USA

[7] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37235 USA

[8] Vanderbilt Univ, Dept Elect & Comp Engn, Nashville, TN USA

[9] Vanderbilt Univ, Dept Comp Sci, Nashville, TN USA

[10] Vanderbilt Univ, Sch Med, Program Canc Biol, Nashville, TN 37235 USA

[11] Vanderbilt Univ, Med Ctr, Ctr Mucosal Inflammat & Canc, Nashville, TN 37235 USA

[12] Vet Affairs Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA

[13] Vanderbilt Univ, Dept Surg, Med Ctr, Nashville, TN 37240 USA

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

基金：

美国国家卫生研究院;

关键词：

NITRIC-OXIDE SYNTHASE; INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; EXPRESSION; SUSCEPTIBILITY; ISOFORMS; SUBSETS; COLON; RISK;

D O I：

10.1038/s41467-024-51580-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：19

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