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Related Experiment Video

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IL-15 Promotes Inflammatory Th17 Cells in the Intestine.

Guoqing Hou1, Allen Lee1, Jonathan L Golob2

  • 1Division of Gastroenterology, University of Michigan, Ann Arbor, MI, United States.

Inflammatory Bowel Diseases
|November 9, 2025
PubMed
Summary
This summary is machine-generated.

Interleukin-15 (IL-15) activates inflammatory T helper 17 (Th17) cells in the colon, offering a potential new treatment target for ulcerative colitis (UC) patients unresponsive to current therapies.

Keywords:
IL-15InflammatoryPathogenicTh17Ulcerative Colitis

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Area of Science:

  • Gastroenterology and Immunology
  • Inflammatory Bowel Disease Research
  • Molecular and Cellular Biology

Background:

  • Ulcerative colitis (UC) is a chronic condition with significant morbidity, where 10-25% of patients lack response to existing treatments, necessitating novel therapeutic strategies.
  • T helper 17 (Th17) cells are implicated in UC pathogenesis and are key targets for current medications.
  • The intestinal microenvironment harbors specialized T cell subsets, suggesting a focus on tissue-resident cytokines regulating these cells.

Purpose of the Study:

  • To investigate cytokines regulating pathogenic T cells within the intestinal microenvironment in ulcerative colitis (UC).
  • To explore the role of the Interleukin-15 (IL-15) axis in the context of UC and its association with pathogenic T cells.

Main Methods:

  • Analysis of public sequencing datasets to identify upregulated cytokine axes in UC.
  • Validation using murine models and human biospecimens to confirm the expression of IL-2 receptor beta (IL-2RB) on pathogenic Th17 cells.
  • Investigating the mechanism of IL-15 activation on Th17 cells in the colon, including JAK1 dependency.

Main Results:

  • The IL-15 axis was found to be upregulated in ulcerative colitis (UC).
  • CD4+ T cells expressing IL-2RB showed a pathogenic Th17 signature in UC.
  • IL-15 activates terminally differentiated Th17 cells in the colon via a JAK1-dependent pathway, independent of Th17 differentiation.

Conclusions:

  • The IL-15 axis is upregulated in UC, and IL-15 activates inflammatory Th17 cells in the colon.
  • IL-15 represents a potential therapeutic target for ulcerative colitis, particularly for patients with refractory disease.