دورية أكاديمية
The TNFSF12/TWEAK Modulates Colonic Inflammatory Fibroblast Differentiation and Promotes Fibroblast-Monocyte Interactions.
العنوان: | The TNFSF12/TWEAK Modulates Colonic Inflammatory Fibroblast Differentiation and Promotes Fibroblast-Monocyte Interactions. |
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المؤلفون: | Matellan C; School of Biomolecular and Biomedical Sciences, University College Dublin, Belfield, Dublin, Ireland.; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.; School of Medicine, Conway Institute of Biomolecular and biomedical Research, University College Dublin, Belfield, Dublin, Ireland., Kennedy C; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.; School of Medicine, Conway Institute of Biomolecular and biomedical Research, University College Dublin, Belfield, Dublin, Ireland.; Diabetes Complications Research Centre, University College Dublin, Belfield, Dublin, Ireland., Santiago-Vela MI; School of Biomolecular and Biomedical Sciences, University College Dublin, Belfield, Dublin, Ireland.; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland., Hochegger J; School of Biomolecular and Biomedical Sciences, University College Dublin, Belfield, Dublin, Ireland.; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland., Ní Chathail MB; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.; School of Public Health, Physiotherapy, and Sports Science, University College Dublin, Belfield, Dublin, Ireland., Wu A; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA., Shannon C; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.; School of Medicine, Conway Institute of Biomolecular and biomedical Research, University College Dublin, Belfield, Dublin, Ireland., Roche HM; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.; School of Public Health, Physiotherapy, and Sports Science, University College Dublin, Belfield, Dublin, Ireland.; Institute for Global Food Security, Queen's University Belfast, Belfast, U.K., Aceves SS; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA.; Rady Children's Hospital, San Diego, CA., Godson C; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.; School of Medicine, Conway Institute of Biomolecular and biomedical Research, University College Dublin, Belfield, Dublin, Ireland.; Diabetes Complications Research Centre, University College Dublin, Belfield, Dublin, Ireland., Manresa MC; School of Biomolecular and Biomedical Sciences, University College Dublin, Belfield, Dublin, Ireland.; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland. |
المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Jun 15; Vol. 212 (12), pp. 1958-1970. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
مواضيع طبية MeSH: | Cytokine TWEAK*/metabolism , Monocytes*/immunology , Monocytes*/metabolism , Fibroblasts*/metabolism , Fibroblasts*/immunology , Colon*/immunology , Colon*/pathology , Colon*/metabolism , Cell Differentiation*/immunology, Humans ; Cell Communication/immunology ; Inflammation/immunology ; THP-1 Cells ; Coculture Techniques ; Cytokines/metabolism ; Cell Adhesion |
مستخلص: | Fibroblasts acquire a proinflammatory phenotype in inflammatory bowel disease, but the factors driving this process and how fibroblasts contribute to mucosal immune responses are incompletely understood. TNF superfamily member 12 (TNFSF12, or TNF-like weak inducer of apoptosis [TWEAK]) has gained interest as a mediator of chronic inflammation. In this study, we explore its role as a driver of inflammatory responses in fibroblasts and its contribution to fibroblast-monocyte interaction using human primary colonic fibroblasts, THP-1 and primary monocytes. Recombinant human TWEAK induced the expression of cytokines, chemokines, and immune receptors in primary colonic fibroblasts. The TWEAK upregulated transcriptome shared 29% homology with a previously published transcriptional profile of inflammatory fibroblasts from ulcerative colitis. TWEAK elevated surface expression of activated fibroblast markers and adhesion molecules (podoplanin [PDPN], ICAM-1, and VCAM-1) and secretion of IL-6, CCL2, and CXCL10. In coculture, fibroblasts induced monocyte adhesion and secretion of CXCL1 and IL-8, and they promoted a CD14high/ICAM-1high phenotype in THP-1 cells, which was enhanced when fibroblasts were prestimulated with TWEAK. Primary monocytes in coculture with TWEAK-treated fibroblasts had altered surface expression of CD16 and triggering receptor expressed on myeloid cells-1 (TREM-1) as well as increased CXCL1 and CXCL10 secretion. Conversely, inhibition of the noncanonical NF-κB pathway on colonic fibroblasts with a NF-κB-inducing kinase small molecule inhibitor impaired their ability to induce a CD14high phenotype on monocytes. Our results indicate that TWEAK promotes an inflammatory fibroblast-monocyte crosstalk that may be amenable for therapeutic intervention. (Copyright © 2024 by The American Association of Immunologists, Inc.) |
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معلومات مُعتمدة: | 21/PATH-S/9621 Science Foundation Ireland (SFI); 15/US/B3130 Science Foundation Ireland (SFI); 15/IA/3152 Science Foundation Ireland (SFI); GOIPD/2023/1118 Irish Research Council (An Chomhairle um Thaighde in Éirinn) |
المشرفين على المادة: | 0 (Cytokine TWEAK) 0 (TNFSF12 protein, human) 0 (Cytokines) |
تواريخ الأحداث: | Date Created: 20240503 Date Completed: 20240603 Latest Revision: 20240611 |
رمز التحديث: | 20240611 |
مُعرف محوري في PubMed: | PMC11149899 |
DOI: | 10.4049/jimmunol.2300762 |
PMID: | 38700420 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1550-6606 |
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DOI: | 10.4049/jimmunol.2300762 |