A unique intestinal epithelial cell that expresses canonical lymphoid genes
8 affiliations
- 1Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
- 2Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
- 3Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
- 4Graduate Program in Genetics, State University of New York, Stony Brook, NY 11794, USA.
- 5Division of Gastroenterology, Hepatology, and Nutrition, Boston Children’s Hospital, Boston, MA 02115, USA.
- 6Section of Surgical Sciences, Epithelial Biology Center, and Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, and Nashville VA Medical Center, Nashville, TN 37212, USA.
- 7Molecular Imaging Core and Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
- 8Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Abstract
Enterocytes and intestinal secretory cells harbor innate immunity. However, certain transcriptional programs -even beyond rearranged T- and B-cell receptor genes- are considered the exclusive purview of adaptive immune cells, including abundant and diverse intestinal intra-epithelial lymphocytes (IELs). Here, we identify and characterize columnar intestinal secretory cells that co-express classic epithelial and lymphoid genes, including Ptprc, Cd3e, Cd8a, and Gzma/b but not T- or B-cell receptors. These previously unrecognized epithelium-derived lymphoid-like cells (EDLCs) differ from any known resident cell type, including IELs or tuft cells. Rare in healthy mouse and human intestines, their numbers increase upon IL-25 stimulation or IL-10 receptor deficiency in vivo and upon IL-13 stimulation in vitro. EDLC chromatin is uniquely accessible at thousands of cis-elements, including lymphoid and epithelial loci. These findings reveal a transcriptionally and epigenetically distinct intestinal epithelial derivative that expresses prominent lymphoid character.
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BibTeX
@misc{bhattacharya2026unique,
title = {{A unique intestinal epithelial cell that expresses canonical lymphoid genes}},
author = {Swarnabh Bhattacharya and Krithika Badarinath and Guodong Tie and Pratik N. P. Singh and Onur Eskiocak and Ruiyang He and Bin Bao and Su-Hyung Lee and Scott Snapper and Kun Huang and James R. Goldenring and Semir Beyaz and Ramesh A. Shivdasani},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.21.760658},
url = {https://www.biorxiv.org/content/10.64898/2026.10.21.760658v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A unique intestinal epithelial cell that expresses canonical lymphoid genes
AU - Swarnabh Bhattacharya
AU - Krithika Badarinath
AU - Guodong Tie
AU - Pratik N. P. Singh
AU - Onur Eskiocak
AU - Ruiyang He
AU - Bin Bao
AU - Su-Hyung Lee
AU - Scott Snapper
AU - Kun Huang
AU - James R. Goldenring
AU - Semir Beyaz
AU - Ramesh A. Shivdasani
PY - 2026
DA - 2026/10/21
PB - bioRxiv
DO - 10.64898/2026.10.21.760658
UR - https://www.biorxiv.org/content/10.64898/2026.10.21.760658v1
AB - Enterocytes and intestinal secretory cells harbor innate immunity. However, certain transcriptional programs -even beyond rearranged T- and B-cell receptor genes- are considered the exclusive purview of adaptive immune cells, including abundant and diverse intestinal intra-epithelial lymphocytes (IELs). Here, we identify and characterize columnar intestinal secretory cells that co-express classic epithelial and lymphoid genes, including Ptprc, Cd3e, Cd8a, and Gzma/b but not T- or B-cell receptors. These previously unrecognized epithelium-derived lymphoid-like cells (EDLCs) differ from any known resident cell type, including IELs or tuft cells. Rare in healthy mouse and human intestines, their numbers increase upon IL-25 stimulation or IL-10 receptor deficiency in vivo and upon IL-13 stimulation in vitro. EDLC chromatin is uniquely accessible at thousands of cis-elements, including lymphoid and epithelial loci. These findings reveal a transcriptionally and epigenetically distinct intestinal epithelial derivative that expresses prominent lymphoid character.
SN - 2692-8205
ER -