The role of intraepithelial lymphocytes in inflammatory bowel disease

Einleitung Intraepithelial lymphocytes (IELs) are T cells that patrol within the epithelial layer of the intestine [1]. IELs represent a first line of defense against pathogens and are mainly antigen-experienced CD8+T cells. Previous work suggested that overreaction or dysfunction of IELs might contribute to the pathogenesis of inflammatory bowel diseases (IBD). CXCL10 is a chemokine considered to promote the recruitment of immune cells to sites of inflammation, thereby amplifying local inflammation. However, the interaction of CXCL10 with IELs from IBD patients has not been clarified so far.

Material und Methodik Primary IELs and intestinal epithelial organoids (IECs) were freshly purified from mucosal biopsies obtained from IBD patients with different inflammatory activity during routine colonoscopy of the terminal ileum. Molecular features and gene expression studies of IELs were performed by various readouts including quantitative PCR, flow cytometry, and confocal microscopy upon immunofluorescent stainings. Further molecular analyses were done in silico with help of the recently established IBD patient database IBDome.

Ergebnisse Molecular in vitro studies revealed that CXCL10 was highly inducible in human IECs, especially upon combined stimulation with IFNγ and TNFα. A positive correlation was found in patients with IBD between the degree of inflammation and the expression of CXCL10. In addition, autologous co-culture setups with IELs and IECs confirmed increased expression of CXCL10 on RNA and protein level in IBD patients with gut inflammation as compared to patients without active inflammation. Correspondingly, we noticed that IELs from the majority of patients with high inflammation produced large amounts of IFNγ and TNFα as compared to control patients. Moreover, lower CXCL10 levels were noticed in patients with anti-TNF treatment as compared to patients without anti-TNF therapy.

Zusammenfassung Our study provided evidence for the dysregulation of a molecular axis involving IFNγ/TNFα and CXCL10 in IELs-IEC crosstalk from patients with IBD and active inflammation. Future studies are needed to further clarify the function and pathophysiological actions of IELs in health and disease which might then enable the development of novel therapeutic options for patients with IBD.

Publikationsverlauf

Artikel online veröffentlicht:
09. März 2023

• Literatur

• 1 Enderle K., Dinkel M., Spath E.-M., Schmid B., Zundler S., Tripal P., Neurath M.F., Hildner K., Neufert C. Dynamic Imaging of IEL-IEC Co-Cultures Allows for Quantification of CD103-Dependent T Cell Migration. Int. J. Mol. Sci 2021; 22: 5148