TY - JOUR
T1 - Single-cell analyses of Crohn’s disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions
AU - Jaeger, Natalia
AU - Gamini, Ramya
AU - Cella, Marina
AU - Schettini, Jorge L.
AU - Bugatti, Mattia
AU - Zhao, Shanrong
AU - Rosadini, Charles V.
AU - Esaulova, Ekaterina
AU - Di Luccia, Blanda
AU - Kinnett, Baylee
AU - Vermi, William
AU - Artyomov, Maxim N.
AU - Wynn, Thomas A.
AU - Xavier, Ramnik J.
AU - Jelinsky, Scott A.
AU - Colonna, Marco
N1 - Funding Information:
R.G., S.Z., J.S., C.V.R., T.A.W., and S.A.J. are Pfizer employees. M.Co. received funding from Pfizer to study ILC biology in Inflammatory Bowel Disease. The remaining authors declare no competing interests.
Funding Information:
We thank the Genome Technology Access Center at the McDonnel Genome Institute at Washington University for scRNA-seq on the 10X platform. The center is supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). We thank E. Lantelme and D. Brinja and the Pathology and Immunology Flow Cytometry Core for cell sorting. We thank D. Bender, R. Lin, and S. Oh and the Center for Human Immunology at Washington University for help in processing the samples for mass cytometry and for advice on analysis. We thank the Washington University Digestive Disease Research Core (NIDDK P30 DK052574) for support. Author R.G. thanks Eric Fauman for supporting the completion of this work. N.J. was partly supported by the Lucille P. Markey Special Emphasis Pathway in Human Pathobiology. This work was in part supported by grants UO1 AI095542, RO1 DE025884, RO1 AI134035, RO1 DK124699, and U19 AI142733 (to MCo).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Crohn’s disease (CD) is a chronic transmural inflammation of intestinal segments caused by dysregulated interaction between microbiome and gut immune system. Here, we profile, via multiple single-cell technologies, T cells purified from the intestinal epithelium and lamina propria (LP) from terminal ileum resections of adult severe CD cases. We find that intraepithelial lymphocytes (IEL) contain several unique T cell subsets, including NKp30+γδT cells expressing RORγt and producing IL-26 upon NKp30 engagement. Further analyses comparing tissues from non-inflamed and inflamed regions of patients with CD versus healthy controls show increased activated TH17 but decreased CD8+T, γδT, TFH and Treg cells in inflamed tissues. Similar analyses of LP find increased CD8+, as well as reduced CD4+T cells with an elevated TH17 over Treg/TFH ratio. Our analyses of CD tissues thus suggest a potential link, pending additional validations, between transmural inflammation, reduced IEL γδT cells and altered spatial distribution of IEL and LP T cell subsets.
AB - Crohn’s disease (CD) is a chronic transmural inflammation of intestinal segments caused by dysregulated interaction between microbiome and gut immune system. Here, we profile, via multiple single-cell technologies, T cells purified from the intestinal epithelium and lamina propria (LP) from terminal ileum resections of adult severe CD cases. We find that intraepithelial lymphocytes (IEL) contain several unique T cell subsets, including NKp30+γδT cells expressing RORγt and producing IL-26 upon NKp30 engagement. Further analyses comparing tissues from non-inflamed and inflamed regions of patients with CD versus healthy controls show increased activated TH17 but decreased CD8+T, γδT, TFH and Treg cells in inflamed tissues. Similar analyses of LP find increased CD8+, as well as reduced CD4+T cells with an elevated TH17 over Treg/TFH ratio. Our analyses of CD tissues thus suggest a potential link, pending additional validations, between transmural inflammation, reduced IEL γδT cells and altered spatial distribution of IEL and LP T cell subsets.
UR - http://www.scopus.com/inward/record.url?scp=85103410614&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-22164-6
DO - 10.1038/s41467-021-22164-6
M3 - Article
C2 - 33771991
AN - SCOPUS:85103410614
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1921
ER -