Integrin β1 Optimizes Diabetogenic T Cell Migration and Function in the Pancreas
Year: 2018
Type: article
Abstract: T cell search behavior is dictated by their need to encounter their specific antigen to eliminate target cells. However, mechanisms controlling effector T cell motility are highly tissue-dependent. Specifically, how diabetogenic T cells encounter their target beta cells in dispersed islets throughout the pancreas during autoimmune diabetes remains unclear. Using intra-vital 2-photon microscopy in a mouse model of diabetes, we found that CXCR3 chemokine downregulated CD8+ T cell motility specifically within islets, promoting effector cell confinement to their target sites. In contrast, T cell velocity and directionality in the exocrine tissue were enhanced along blood vessels and extra-cellular matrix fibers. This guided migration implicated integrin-dependent interactions, since integrin blockade impaired exocrine T cell motility. In addition, integrin β1 blockade decreased CD4+ T cell effector phenotype specifically in the pancreas. Thus, we unveil an important role for integrins in the pancreas during autoimmune diabetes that may have important implications for the design of new therapies.
Source: Frontiers in Immunology
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Awards: G2861269148, G381665449, G5944851057, Vascular and cellular dynamics in pancreatic islets during type 1 diabetes, G7240651115, G7356045907, Développment d'une infrastructure française distribuée coordonnée, Transfer of MSC mitochondria to T lymphocytes: impact on T cell metabolism, phenotype and recirculation in autoimmunity
OpenAlex ID: W2952427366