IFNγ induces epithelial reprogramming driving CXCL11-mediated T cell migration.

Autor:	Cutilli A; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands.; Center of Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands., Jansen SA; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands.; Division of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands.; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Paolucci F; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands.; Center of Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands., van Hoesel M; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands.; Division of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands.; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Fredericks CL; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands.; Center of Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands., Mulder TAM; Center of Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands., Chalkiadakis T; Center of Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands., Mokry M; Division of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands.; Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands., Prekovic S; Center of Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands., Mocholi E; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands.; Center of Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands., Lindemans CA; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands.; Division of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands.; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Coffer PJ; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands.; Center of Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.; Division of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of leukocyte biology [J Leukoc Biol] 2024 Sep 20. Date of Electronic Publication: 2024 Sep 20.
DOI:	10.1093/jleuko/qiae205
Abstrakt:	The cytokine interferon-gamma (IFNγ) plays a multifaceted role in intestinal immune responses ranging from anti- to pro-inflammatory depending on the setting. Here, using a 3D co-culture system based on human intestinal epithelial organoids, we explore the capacity of IFNγ-exposure to reprogram intestinal epithelia and thereby directly modulate lymphocyte responses. IFNγ treatment of organoids led to transcriptional reprogramming, marked by a switch to a pro-inflammatory gene expression profile, including transcriptional upregulation of the chemokines CXCL9, CXCL10, and CXCL11. Proteomic analysis of organoid-conditioned medium post-treatment confirmed chemokine secretion. IFNγ-treatment of organoids led to enhanced T cell migration in a CXCL11-dependent manner without affecting T cell activation status. Taken together, our results suggest a specific role for CXCL11 in T cell recruitment that could be targeted to prevent T cell trafficking to the inflamed intestine. (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)
Databáze:	MEDLINE
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