Faculty, Staff and Student Publications
Language
English
Publication Date
10-1-2025
Journal
Mucosal Immunology/
PMCID
PMC12431686
PubMedCentral® Posted Date
9-13-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Patients with autoimmune diseases are more susceptible to foodborne infections, which can be exacerbated by immunosuppressive therapy. Tofacitinib, a JAK/STAT pathway inhibitor, was recently approved for the treatment of ulcerative colitis, yet its effects on the pathogenesis of intestinal infections remain unclear. Here, we examined the impact of oral tofacitinib treatment in a mouse model of Campylobacter jejuni (C. jejuni) infection. Our results show that early tofacitinib administration attenuates intestinal pathology without affecting bacterial colonization. Specifically, tofacitinib suppressed CXCL1, CXCL2, CCL2 chemokine expression by intestinal epithelial cells, limiting recruitment of monocytes and neutrophils to the gut. In addition, JAK/STAT inhibition reduced IFNγ-producing innate lymphoid cells (ILCs) and T cells in the gut. Furthermore, tofacitinib suppressed IFNγ production and ameliorated intestinal disease in humanized mice. Cell-fate mapping revealed that tofacitinib predominantly inhibited IFNγ production by NK1.1
Keywords
Animals, Pyrimidines, Piperidines, Mice, Interferon-gamma, Humans, T-Lymphocytes, Disease Models, Animal, Campylobacter Infections, Campylobacter jejuni, Lymphocytes, Immunity, Innate, Mice, Inbred C57BL, Intestinal Mucosa, Intestines, Signal Transduction, Protein Kinase Inhibitors, Tofacitinib, JAK/STAT, Infectious colitis, Innate lymphoid cells, Campylobacter jejuni
Published Open-Access
yes
Recommended Citation
Korchagina, Anna A; Shein, Sergey A; Muraoka, Wayne T; et al., "Tofacitinib Ameliorates Campylobacter-Induced Intestinal Pathology by Suppressing IFNγ Producing ILCs and T Cells" (2025). Faculty, Staff and Student Publications. 4433.
https://digitalcommons.library.tmc.edu/uthmed_docs/4433