Pancreatic islets communicate with lymphoid tissues via exocytosis of insulin peptides

Nature
Xiaoxiao WanEmil R Unanue

Abstract

Tissue-specific autoimmunity occurs when selected antigens presented by susceptible alleles of the major histocompatibility complex are recognized by T cells. However, the reason why certain specific self-antigens dominate the response and are indispensable for triggering autoreactivity is unclear. Spontaneous presentation of insulin is essential for initiating autoimmune type 1 diabetes in non-obese diabetic mice1,2. A major set of pathogenic CD4 T cells specifically recognizes the 12-20 segment of the insulin B-chain (B:12-20), an epitope that is generated from direct presentation of insulin peptides by antigen-presenting cells3,4. These T cells do not respond to antigen-presenting cells that have taken up insulin that, after processing, leads to presentation of a different segment representing a one-residue shift, B:13-214. CD4 T cells that recognize B:12-20 escape negative selection in the thymus and cause diabetes, whereas those that recognize B:13-21 have only a minor role in autoimmunity3-5. Although presentation of B:12-20 is evident in the islets3,6, insulin-specific germinal centres can be formed in various lymphoid tissues, suggesting that insulin presentation is widespread7,8. Here we use live imaging to document th...Continue Reading

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Citations

Oct 22, 2018·Immunogenetics·Laura Santambrogio, Hans-Georg Rammensee
May 28, 2019·Clinical and Experimental Immunology·T A Wiles, T Delong
Oct 6, 2019·International Immunology·Minoru MatsumotoHitoshi Nishijima
Mar 7, 2020·Molecular & Cellular Proteomics : MCP·Xing-Huang GaoMaria Hatzoglou
May 26, 2020·Advanced Materials·Xudong ZhangZhen Gu
Apr 7, 2020·The Journal of Experimental Medicine·Pavel N ZakharovEmil R Unanue
Apr 7, 2019·Seminars in Immunopathology·Elise Dalmas
Jan 29, 2019·Precision Clinical Medicine·Xiaoxiao Wan, Emil R Unanue
Aug 1, 2018·Nature·Jiajie Wei, Jonathan W Yewdell
Aug 2, 2019·Current Diabetes Reports·Sarita NegiSteven Paraskevas
Apr 2, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emmi-Leena IhantolaTuure Kinnunen
Jul 4, 2020·Current Opinion in Endocrinology, Diabetes, and Obesity·Sefina ArifMartin Eichmann
Apr 24, 2019·Diabetes·Anthony W PurcellTeresa P DiLorenzo
Oct 24, 2020·The Journal of Experimental Medicine·Brendan ReedJohn W Kappler
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Hao HuEmil R Unanue
Dec 10, 2020·Nature Reviews. Endocrinology·Bart O RoepArnaud Zaldumbide
Feb 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Angela M MitchellAaron W Michels
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Xing-Huang GaoMaria Hatzoglou
Feb 2, 2021·Immunology and Cell Biology·Stuart I Mannering, Pushpak Bhattacharjee
Apr 4, 2021·Biomolecules·Yong Kyung KimHoward W Davidson
Apr 7, 2021·The Journal of Experimental Medicine·Anthony N VomundEmil R Unanue
Apr 16, 2021·Frontiers in Immunology·Alexia Carré, Roberto Mallone
Apr 30, 2021·Frontiers in Endocrinology·Henner Zirpel, Bart O Roep
May 15, 2021·Frontiers in Immunology·Brendan K Reed, John W Kappler
May 28, 2021·The Journal of Biological Chemistry·Nitin AmdareTeresa P DiLorenzo
Jun 7, 2021·Current Opinion in Endocrinology, Diabetes, and Obesity·Laura M Jacobsen, Desmond A Schatz
Dec 27, 2018·Journal of Proteome Research·T. Aaron WilesThomas Delong

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Datasets Mentioned

BETA
GSE114824
PXD009919

Methods Mentioned

BETA
transgenic
electron microscopy
ELISA
antibody capture
RNA-seq

Software Mentioned

PEAKS
FlowJo
Imaris
DESeq2
GSEA
AMT Image Capture Engine
Combat
Tree Star

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