Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/16056
Title
Role of endocytosis and trans-endocytosis in ICOS costimulator-induced downmodulation of the ICOS Ligand
Author(s)
Aragoneses-Fenoll, Laura ISCIII | Montes-Casado, Maria ISCIII | Ojeda, Gloria ISCIII | García-Paredes, Lucía | Arimura, Yutaka | Yagi, Junji | Dianzani, Umberto | Portoles, Pilar ISCIII | Rojo, José M
Date issued
2021-11
Citation
J Leukoc Biol. 2021 Nov;110(5):867-884.
Language
Inglés
Document type
journal article
Abstract
The interaction between the T-lymphocyte costimulatory molecule ICOS and its ligand (ICOS-L) is needed for efficient immune responses, but expression levels are tightly controlled, as altered expression of ICOS or ICOS-L may lead to immunodeficiency, or favor autoimmune diseases and tumor growth. Using cells of mouse B cell lymphoma (M12.C3) and melanoma (B16), or hamster CHO cells transfected with various forms of mouse ICOS-L, and ICOS+ T cell lines, we show that, within minutes, ICOS induces significant downmodulation of surface ICOS-L that is largely mediated by endocytosis and trans-endocytosis. So, after interaction with ICOS+ cells, ICOS-L was found inside permeabilized cells, or in cell lysates, with significant transfer of ICOS from ICOS+ T cells to ICOS-L-expressing cells, and simultaneous loss of surface ICOS by the T cells. Data from cells expressing ICOS-L mutants show that conserved, functionally important residues in the cytoplasmic domain of mouse ICOS-L (Arg300 , Ser307 and Tyr308 ), or removal of ICOS-L cytoplasmic tail have minor effect on its internalization. Internalization was dependent on temperature, and was partially dependent on actin polymerization, the GTPase dynamin, protein kinase C, or the integrity of lipid rafts. In fact, a fraction of ICOS-L was detected in lipid rafts. On the other hand, proteinase inhibitors had negligible effects on early modulation of ICOS-L from the cell surface. Our data add a new mechanism of control of ICOS-L expression to the regulation of ICOS-dependent responses.
Subject
MESH
Animals | CHO Cells | Cricetinae | Cricetulus | Down-Regulation | Endocytosis | Inducible T-Cell Co-Stimulator Ligand | Inducible T-Cell Co-Stimulator Protein | Lymphocyte Activation | Melanoma, Experimental | Mice | Mice, Inbred C57BL | Mice, Knockout
Online version
DOI
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