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CD11c+ Cells Are Gatekeepers for Lymphocyte Trafficking to Infiltrated Islets During Type 1 Diabetes.
Sandor, Adam M; Lindsay, Robin S; Dyjack, Nathan; Whitesell, Jennifer C; Rios, Cydney; Bradley, Brenda J; Haskins, Kathryn; Serreze, David V; Geurts, Aron M; Chen, Yi-Guang; Seibold, Max A; Jacobelli, Jordan; Friedman, Rachel S.
Afiliación
  • Sandor AM; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  • Lindsay RS; Department of Biomedical Research, National Jewish Health, Denver, CO, United States.
  • Dyjack N; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  • Whitesell JC; Department of Biomedical Research, National Jewish Health, Denver, CO, United States.
  • Rios C; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, United States.
  • Bradley BJ; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  • Haskins K; Department of Biomedical Research, National Jewish Health, Denver, CO, United States.
  • Serreze DV; Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, United States.
  • Geurts AM; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  • Chen YG; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
  • Seibold MA; The Jackson Laboratory, Bar Harbor, ME, United States.
  • Jacobelli J; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, United States.
  • Friedman RS; Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States.
Front Immunol ; 10: 99, 2019.
Article en En | MEDLINE | ID: mdl-30766536
Type 1 diabetes (T1D) is a T cell mediated autoimmune disease that affects more than 19 million people with incidence increasing rapidly worldwide. For T cells to effectively drive T1D, they must first traffic to the islets and extravasate through the islet vasculature. Understanding the cues that lead to T cell entry into inflamed islets is important because diagnosed T1D patients already have established immune infiltration of their islets. Here we show that CD11c+ cells are a key mediator of T cell trafficking to infiltrated islets in non-obese diabetic (NOD) mice. Using intravital 2-photon islet imaging we show that T cell extravasation into the islets is an extended process, with T cells arresting in the islet vasculature in close proximity to perivascular CD11c+ cells. Antigen is not required for T cell trafficking to infiltrated islets, but T cell chemokine receptor signaling is necessary. Using RNAseq, we show that islet CD11c+ cells express over 20 different chemokines that bind chemokine receptors expressed on islet T cells. One highly expressed chemokine-receptor pair is CXCL16-CXCR6. However, NOD. CXCR6-/- mice progressed normally to T1D and CXCR6 deficient T cells trafficked normally to the islets. Even with CXCR3 and CXCR6 dual deficiency, T cells trafficked to infiltrated islets. These data reinforce that chemokine receptor signaling is highly redundant for T cell trafficking to inflamed islets. Importantly, depletion of CD11c+ cells strongly inhibited T cell trafficking to infiltrated islets of NOD mice. We suggest that targeted depletion of CD11c+ cells associated with the islet vasculature may yield a therapeutic target to inhibit T cell trafficking to inflamed islets to prevent progression of T1D.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T / Islotes Pancreáticos / Antígeno CD11c / Diabetes Mellitus Tipo 1 Límite: Animals Idioma: En Revista: Front Immunol Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T / Islotes Pancreáticos / Antígeno CD11c / Diabetes Mellitus Tipo 1 Límite: Animals Idioma: En Revista: Front Immunol Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza