IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59648-8.html
   My bibliography  Save this article

Single-cell transcriptomic characterization of microscopic colitis

Author

Listed:
  • Stefan Halvorsen

    (Massachusetts General Hospital (MGH))

  • Molly Thomas

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard
    Harvard Medical School (HMS))

  • Mari Mino-Kenudson

    (Harvard Medical School (HMS)
    MGH)

  • Yuko Kinowaki

    (MGH)

  • Kristin E. Burke

    (MGH
    MGH)

  • David Morgan

    (MGH)

  • Kaia C. Miller

    (MGH
    Duke University Health System)

  • Katherine M. Williams

    (MGH)

  • Jenny Gurung

    (MGH)

  • Jessica McGoldrick

    (MGH)

  • Megan Hopton

    (Massachusetts General Hospital (MGH))

  • Brooke Hoppe

    (Massachusetts General Hospital (MGH))

  • Nandini Samanta

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard)

  • Sidney Martin

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard)

  • Alice Tirard

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard)

  • Benjamin Y. Arnold

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard)

  • Jessica Tantivit

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard)

  • Joseph Yarze

    (MGH)

  • Kyle Staller

    (MGH
    MGH)

  • Daniel C. Chung

    (MGH)

  • Alexandra-Chloé Villani

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard
    Harvard Medical School (HMS))

  • Slim Sassi

    (Massachusetts General Hospital (MGH)
    Harvard Medical School (HMS)
    MGH)

  • Hamed Khalili

    (Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard
    MGH
    MGH
    Karolinska Institutet)

Abstract

Microscopic colitis (MC) is a chronic inflammatory disease of the large intestine and a common cause of chronic diarrhea in older adults. Here, we use single-cell RNA sequencing analysis of colonic mucosal tissue to build a cellular and molecular model for MC. Our results show that in MC, there is a substantial expansion of tissue CD8+ T cells, likely arising from local expansion following T cell receptor engagement. Within the T cell compartment, MC is characterized by a shift in CD8 tissue-resident memory T cells towards a highly cytotoxic and inflammatory phenotype and expansion of CD4+ T regulatory cells. These results provide insight into inflammatory cytokines shaping MC pathogenesis and highlight notable similarities and differences with other immune-mediated intestinal diseases, including a common upregulation of IL26 and an MC-specific upregulation of IL10. These data help identify targets against enteric T cell subsets as an effective strategy for treatment of MC.

Suggested Citation

  • Stefan Halvorsen & Molly Thomas & Mari Mino-Kenudson & Yuko Kinowaki & Kristin E. Burke & David Morgan & Kaia C. Miller & Katherine M. Williams & Jenny Gurung & Jessica McGoldrick & Megan Hopton & Bro, 2025. "Single-cell transcriptomic characterization of microscopic colitis," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59648-8
    DOI: 10.1038/s41467-025-59648-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59648-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-59648-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Mayura V. Wagle & Stephin J. Vervoort & Madison J. Kelly & Willem Byl & Timothy J. Peters & Ben P. Martin & Luciano G. Martelotto & Simone Nüssing & Kelly M. Ramsbottom & James R. Torpy & Deborah Kni, 2021. "Antigen-driven EGR2 expression is required for exhausted CD8+ T cell stability and maintenance," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Joyce Chen & Isaac F. López-Moyado & Hyungseok Seo & Chan-Wang J. Lio & Laura J. Hempleman & Takashi Sekiya & Akihiko Yoshimura & James P. Scott-Browne & Anjana Rao, 2019. "NR4A transcription factors limit CAR T cell function in solid tumours," Nature, Nature, vol. 567(7749), pages 530-534, March.
    3. M. Büttner & J. Ostner & C. L. Müller & F. J. Theis & B. Schubert, 2021. "scCODA is a Bayesian model for compositional single-cell data analysis," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    4. Xindong Liu & Yun Wang & Huiping Lu & Jing Li & Xiaowei Yan & Minglu Xiao & Jing Hao & Andrei Alekseev & Hiep Khong & Tenghui Chen & Rui Huang & Jin Wu & Qiwen Zhao & Qi Wu & Senlin Xu & Xiaohu Wang &, 2019. "Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction," Nature, Nature, vol. 567(7749), pages 525-529, March.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Hailyn V. Nielsen & Letitia Yang & James L. Mueller & Alexander J. Ritter & Ryosuke Hiwa & Irina Proekt & Elze Rackaityte & Dominik Aylard & Mansi Gupta & Christopher D. Scharer & Mark S. Anderson & B, 2025. "Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    2. Yi Liu & Brian Debo & Mingfeng Li & Zhennan Shi & Wanqiang Sheng & Yang Shi, 2021. "LSD1 inhibition sustains T cell invigoration with a durable response to PD-1 blockade," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. Alexandria C. Wells & Kaito A. Hioki & Constance C. Angelou & Adam C. Lynch & Xueting Liang & Daniel J. Ryan & Iris Thesmar & Saule Zhanybekova & Saulius Zuklys & Jacob Ullom & Agnes Cheong & Jesse Ma, 2023. "Let-7 enhances murine anti-tumor CD8 T cell responses by promoting memory and antagonizing terminal differentiation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Carli M. Stewart & Elizabeth L. Siegler & R. Leo Sakemura & Michelle J. Cox & Truc Huynh & Brooke Kimball & Long Mai & Ismail Can & Claudia Manriquez Roman & Kun Yun & Olivia Sirpilla & James H. Girsc, 2024. "IL-4 drives exhaustion of CD8+ CART cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Xiaofeng Liao & Wenxue Li & Hongyue Zhou & Barani Kumar Rajendran & Ao Li & Jingjing Ren & Yi Luan & David A. Calderwood & Benjamin Turk & Wenwen Tang & Yansheng Liu & Dianqing Wu, 2024. "The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    6. Jonas Engesser & Robin Khatri & Darius P. Schaub & Yu Zhao & Hans-Joachim Paust & Zeba Sultana & Nariaki Asada & Jan-Hendrik Riedel & Varshi Sivayoganathan & Anett Peters & Anna Kaffke & Saskia-Lariss, 2024. "Immune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    7. Brian R. Lindman & Andrew S. Perry & Michelle L. Lance & Kaushik Amancherla & Namju Kim & Quanhu Sheng & Phillip Lin & Ryan D. Pfeiffer & Eric Farber-Eger & William F. Fearon & Samir Kapadia & Dharam , 2025. "Integrated multiomics of pressure overload in the human heart prioritizes targets relevant to heart failure," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    8. Yi Huang & Anyongqi Wang & Wenjiang Zhou & Baoguo Li & Linshan Zhang & Agata M. Rudolf & Zengguang Jin & Catherine Hambly & Guanlin Wang & John R. Speakman, 2024. "Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Hao Wu & Xiufeng Zhao & Sophia M. Hochrein & Miriam Eckstein & Gabriela F. Gubert & Konrad Knöpper & Ana Maria Mansilla & Arman Öner & Remi Doucet-Ladevèze & Werner Schmitz & Bart Ghesquière & Sebasti, 2023. "Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. Davide Pisu & Luana Johnston & Joshua T. Mattila & David G. Russell, 2024. "The frequency of CD38+ alveolar macrophages correlates with early control of M. tuberculosis in the murine lung," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    11. Matthew C. Hill & Bridget Simonson & Carolina Roselli & Ling Xiao & Caroline N. Herndon & Mark Chaffin & Helene Mantineo & Ondine Atwa & Harshit Bhasin & Yasmine Guedira & Kenneth C. Bedi & Kenneth B., 2024. "Large-scale single-nuclei profiling identifies role for ATRNL1 in atrial fibrillation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    12. Zhenlin Yang & He Tian & Xiaowei Chen & Bozhao Li & Guangyu Bai & Qingyuan Cai & Jiachen Xu & Wei Guo & Shuaibo Wang & Yue Peng & Qing Liang & Liyan Xue & Shugeng Gao, 2024. "Single-cell sequencing reveals immune features of treatment response to neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    13. Kaya J. E. Matson & Daniel E. Russ & Claudia Kathe & Isabelle Hua & Dragan Maric & Yi Ding & Jonathan Krynitsky & Randall Pursley & Anupama Sathyamurthy & Jordan W. Squair & Boaz P. Levi & Gregoire Co, 2022. "Single cell atlas of spinal cord injury in mice reveals a pro-regenerative signature in spinocerebellar neurons," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    14. Jessy A. Slota & Lise Lamoureux & Kathy L. Frost & Babu V. Sajesh & Stephanie A. Booth, 2024. "Single-cell transcriptomics unveils molecular signatures of neuronal vulnerability in a mouse model of prion disease that overlap with Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    15. Ivan V. Kuzmin & Ruben Soto Acosta & Layne Pruitt & Perry T. Wasdin & Kritika Kedarinath & Keziah R. Hernandez & Kristyn A. Gonzales & Kharighan Hill & Nicole G. Weidner & Chad Mire & Taylor B. Engdah, 2024. "Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    16. Sebastian Schmidt & Malte D. Luecken & Dietrich Trümbach & Sina Hembach & Kristina M. Niedermeier & Nicole Wenck & Klaus Pflügler & Constantin Stautner & Anika Böttcher & Heiko Lickert & Ciro Ramirez-, 2022. "Primary cilia and SHH signaling impairments in human and mouse models of Parkinson’s disease," Nature Communications, Nature, vol. 13(1), pages 1-25, December.
    17. Songren Wei & Meng Luo & Pingping Wang & Rui Chen & Xiyun Jin & Chang Xu & Chenyang Li & Xiaoyu Lin & Zhaochun Xu & Hongxin Liu & Rui Cheng & Wenyi Yang & Yideng Cai & Guangfu Xue & Peng Huang & Zhiga, 2025. "Charting the spatial transcriptome of the human cerebral cortex at single-cell resolution," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    18. Andrew Gibson & Ramesh Ram & Rama Gangula & Yueran Li & Eric Mukherjee & Amy M. Palubinsky & Chelsea N. Campbell & Michael Thorne & Katherine C. Konvinse & Phuti Choshi & Pooja Deshpande & Sarah Pedre, 2024. "Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson syndrome and toxic epidermal necrolysis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    19. Evelyn Chang & Kelly Cavallo & Samuel M. Behar, 2025. "CD4 T cell dysfunction is associated with bacterial recrudescence during chronic tuberculosis," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    20. Drew R. Neavin & Angela M. Steinmann & Nona Farbehi & Han Sheng Chiu & Maciej S. Daniszewski & Himanshi Arora & Yasmin Bermudez & Cátia Moutinho & Chia-Ling Chan & Monique Bax & Mubarika Tyebally & Vi, 2023. "A village in a dish model system for population-scale hiPSC studies," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59648-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.