Spatiotemporal regulation of galectin-1-induced T-cell death in lamina propria from Crohn's disease and ulcerative colitis patients.

Autor: Papa-Gobbi R; Instituto de Estudios Inmunológicos y Fisiopatológicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), La Plata, Argentina.; Transplant Group, La Paz University Hospital Health Research Institute (IdiPAZ), Madrid, Spain., Muglia CI; Instituto de Estudios Inmunológicos y Fisiopatológicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), La Plata, Argentina., Rocca A; Servicio de Colonoscopia, Hospital de Gastroenterología Dr. Bonorino Udaondo, Buenos Aires, Argentina., Curciarello R; Instituto de Estudios Inmunológicos y Fisiopatológicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), La Plata, Argentina., Sambuelli AM; Servicio de Enfermedades Inflamatorias, Hospital Dr. Bonorino Udaondo, Buenos Aires, Argentina., Yantorno M; Servicio de Colonoscopia, Hospital San Martin, La Plata, Argentina., Correa G; Servicio de Colonoscopia, Hospital San Martin, La Plata, Argentina., Morosi LG; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 1428, Buenos Aires, Argentina.; Laboratorio de Glicómica Funcional y Molecular, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 1428, Buenos Aires, Argentina., Di Sabatino A; First Department of Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy., Biancheri P; Department of Gastroenterology, Norfolk and Norwich University Hospital, Norwich Medical School, University of East Anglia, Norwich, UK., MacDonald TT; Centre for Immunobiology, Barts and The London School of Medicine and Dentistry, London, UK., Toscano MA; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 1428, Buenos Aires, Argentina., Mariño KV; Laboratorio de Glicómica Funcional y Molecular, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 1428, Buenos Aires, Argentina., Rabinovich GA; Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 1428, Buenos Aires, Argentina.; Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428, Buenos Aires, Argentina., Docena GH; Instituto de Estudios Inmunológicos y Fisiopatológicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), La Plata, Argentina. guidoc@biol.unl.edu.ar.
Jazyk: angličtina
Zdroj: Apoptosis : an international journal on programmed cell death [Apoptosis] 2021 Jun; Vol. 26 (5-6), pp. 323-337. Date of Electronic Publication: 2021 May 12.
DOI: 10.1007/s10495-021-01675-z
Abstrakt: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic, relapsing intestinal inflammation. Galectin-1 (Gal-1) is an endogenous lectin with key pro-resolving roles, including induction of T-cell apoptosis and secretion of immunosuppressive cytokines. Despite considerable progress, the relevance of Gal-1-induced T-cell death in inflamed tissue from human IBD patients has not been ascertained. Intestinal biopsies and surgical specimens from control patients (n = 52) and patients with active or inactive IBD (n = 97) were studied. Gal-1 expression was studied by RT-qPCR, immunoblotting, ELISA and immunohistochemistry. Gal-1-specific ligands and Gal-1-induced apoptosis of lamina propria (LP) T-cells were determined by TUNEL and flow cytometry. We found a transient expression of asialo core 1-O-glycans in LP T-cells from inflamed areas (p < 0.05) as revealed by flow cytometry using peanut agglutinin (PNA) binding and assessing dysregulation of the core-2 β 1-6-N-acetylglucosaminyltransferase 1 (C2GNT1), an enzyme responsible for elongation of core 2 O-glycans. Consequently, Gal-1 binding was attenuated in CD3 + CD4 + and CD3 + CD8 + LP T-cells isolated from inflamed sites (p < 0.05). Incubation with recombinant Gal-1 induced apoptosis of LP CD3 + T-cells isolated from control subjects and non-inflamed areas of IBD patients (p < 0.05), but not from inflamed areas. In conclusion, our findings showed that transient regulation of the O-glycan profile during inflammation modulates Gal-1 binding and LP T-cell survival in IBD patients.
Databáze: MEDLINE
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