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Landscape of Interactions between Stromal and Myeloid Cells in Ileal Crohn's Disease; Indications of an Important Role for Fibroblast-Derived CCL-2.
Dovrolis, Nikolas; Valatas, Vassilis; Drygiannakis, Ioannis; Filidou, Eirini; Spathakis, Michail; Kandilogiannakis, Leonidas; Tarapatzi, Gesthimani; Arvanitidis, Konstantinos; Bamias, Giorgos; Vradelis, Stergios; Manolopoulos, Vangelis G; Paspaliaris, Vasilis; Kolios, George.
Afiliação
  • Dovrolis N; Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
  • Valatas V; Individualised Medicine & Pharmacological Research Solutions Center (IMPReS), 68100 Alexandroupolis, Greece.
  • Drygiannakis I; Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
  • Filidou E; Gastroenterology and Hepatology Research Laboratory, Medical School, University of Crete, 71003 Heraklion, Greece.
  • Spathakis M; Gastroenterology and Hepatology Research Laboratory, Medical School, University of Crete, 71003 Heraklion, Greece.
  • Kandilogiannakis L; Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
  • Tarapatzi G; Individualised Medicine & Pharmacological Research Solutions Center (IMPReS), 68100 Alexandroupolis, Greece.
  • Arvanitidis K; Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
  • Bamias G; Individualised Medicine & Pharmacological Research Solutions Center (IMPReS), 68100 Alexandroupolis, Greece.
  • Vradelis S; Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
  • Manolopoulos VG; Individualised Medicine & Pharmacological Research Solutions Center (IMPReS), 68100 Alexandroupolis, Greece.
  • Paspaliaris V; Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
  • Kolios G; Individualised Medicine & Pharmacological Research Solutions Center (IMPReS), 68100 Alexandroupolis, Greece.
Biomedicines ; 12(8)2024 Jul 26.
Article em En | MEDLINE | ID: mdl-39200138
ABSTRACT
BACKGROUND AND

AIMS:

Monocyte recruitment in the lamina propria and inflammatory phenotype driven by the mucosal microenvironment is critical for the pathogenesis of inflammatory bowel disease. However, the stimuli responsible remain largely unknown. Recent works have focused on stromal cells, the main steady-state cellular component in tissue, as they produce pro-inflammatory chemokines that contribute to the treatment-resistant nature of IBD.

METHODS:

We studied the regulation of these processes by examining the communication patterns between stromal and myeloid cells in ileal Crohn's disease (CD) using a complete single-cell whole tissue sequencing analysis pipeline and in vitro experimentation in mesenchymal cells.

RESULTS:

We report expansion of S4 stromal cells and monocyte-like inflammatory macrophages in the inflamed mucosa and describe interactions that may establish sustained local inflammation. These include expression of CCL2 by S1 fibroblasts to recruit and retain monocytes and macrophages in the mucosa, where they receive signals for proliferation, survival, and differentiation to inflammatory macrophages from S4 stromal cells through molecules such as MIF, IFNγ, and FN1. The overexpression of CCL2 in ileal CD and its stromal origin was further demonstrated in vitro by cultured mesenchymal cells and intestinal organoids in the context of an inflammatory milieu.

CONCLUSIONS:

Our findings outline an extensive cross-talk between stromal and myeloid cells, which may contribute to the onset and progression of inflammation in ileal Crohn's disease. Understanding the mechanisms underlying monocyte recruitment and polarization, as well as the role of stromal cells in sustaining inflammation, can provide new avenues for developing targeted therapies to treat IBD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Biomedicines Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Grécia País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Biomedicines Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Grécia País de publicação: Suíça