PMID- 37734713
OWN - NLM
STAT- MEDLINE
DCOM- 20231128
LR  - 20240210
IS  - 2212-8778 (Electronic)
IS  - 2212-8778 (Linking)
VI  - 78
DP  - 2023 Dec
TI  - The beta cell-immune cell interface in type 1 diabetes (T1D).
PG  - 101809
LID - S2212-8778(23)00143-6 [pii]
LID - 10.1016/j.molmet.2023.101809 [doi]
LID - 101809
AB  - BACKGROUND: T1D is an autoimmune disease in which pancreatic islets of Langerhans 
      are infiltrated by immune cells resulting in the specific destruction of 
      insulin-producing islet beta cells. Our understanding of the factors leading to 
      islet infiltration and the interplay of the immune cells with target beta cells 
      is incomplete, especially in human disease. While murine models of T1D have 
      provided crucial information for both beta cell and autoimmune cell function, the 
      translation of successful therapies in the murine model to human disease has been 
      a challenge. SCOPE OF REVIEW: Here, we discuss current state of the art and 
      consider knowledge gaps concerning the interface of the islet beta cell with 
      immune infiltrates, with a focus on T cells. We discuss pancreatic and immune 
      cell phenotypes and their impact on cell function in health and disease, which we 
      deem important to investigate further to attain a more comprehensive 
      understanding of human T1D disease etiology. MAJOR CONCLUSIONS: The last years 
      have seen accelerated development of approaches that allow comprehensive study of 
      human T1D. Critically, recent studies have contributed to our revised 
      understanding that the pancreatic beta cell assumes an active role, rather than a 
      passive position, during autoimmune disease progression. The T cell-beta cell 
      interface is a critical axis that dictates beta cell fate and shapes autoimmune 
      responses. This includes the state of the beta cell after processing internal and 
      external cues (e.g., stress, inflammation, genetic risk) that that contributes to 
      the breaking of tolerance by hyperexpression of human leukocyte antigen (HLA) 
      class I with presentation of native and neoepitopes and secretion of chemotactic 
      factors to attract immune cells. We anticipate that emerging insights about the 
      molecular and cellular aspects of disease initiation and progression processes 
      will catalyze the development of novel and innovative intervention points to 
      provide additional therapies to individuals affected by T1D.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.
FAU - James, Eddie A
AU  - James EA
AD  - Center for Translational Immunology, Benaroya Research Institute, Seattle, WA, 
      USA.
FAU - Joglekar, Alok V
AU  - Joglekar AV
AD  - Center for Systems Immunology and Department of Immunology, University of 
      Pittsburgh School of Medicine, Pittsburgh, PA, USA.
FAU - Linnemann, Amelia K
AU  - Linnemann AK
AD  - Center for Diabetes and Metabolic Diseases, and Herman B Wells Center for 
      Pediatric Research, Department of Pediatrics, Indiana University School of 
      Medicine, Indianapolis, IN, USA.
FAU - Russ, Holger A
AU  - Russ HA
AD  - Diabetes Institute, University of Florida, Gainesville, FL, USA; Department of 
      Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA.
FAU - Kent, Sally C
AU  - Kent SC
AD  - Diabetes Center of Excellence, Department of Medicine, University of 
      Massachusetts Chan Medical School, Worcester, MA, USA. Electronic address: 
      sally.kent@umassmed.edu.
LA  - eng
GR  - P30 DK097512/DK/NIDDK NIH HHS/United States
GR  - R03 DK127766/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20230920
PL  - Germany
TA  - Mol Metab
JT  - Molecular metabolism
JID - 101605730
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Diabetes Mellitus, Type 1/metabolism
MH  - *Insulin-Secreting Cells/metabolism
MH  - *Islets of Langerhans/metabolism
MH  - Pancreas/metabolism
MH  - Risk Factors
PMC - PMC10622886
OTO - NOTNLM
OT  - Beta cells
OT  - Islets
OT  - Neoepitopes
OT  - T cell infiltrates
OT  - Tolerance
OT  - Type 1 diabetes
COIS- Declaration of competing interest AKL has been on a scientific advisory panel for 
      Janssen Research & Development, LLC. AVJ has been a consultant for Pfizer Inc. 
      and has received research funding from Mitsubishi-Tanabe Pharma. EAJ has been a 
      consultant for ProventionBio and has research projects sponsored by Bristol-Myers 
      Squibb and Novartis. HAR has been a SAB member for Prellis Biologics and Sigilon 
      Therapeutics and consultant to Eli Lilly, Minutia, Guidepoint, and Axon. SCK is 
      an SAB member for 4Immune Therapeutics.
EDAT- 2023/09/22 00:42
MHDA- 2023/11/28 06:42
PMCR- 2023/09/20
CRDT- 2023/09/21 19:19
PHST- 2023/07/01 00:00 [received]
PHST- 2023/09/01 00:00 [revised]
PHST- 2023/09/15 00:00 [accepted]
PHST- 2023/11/28 06:42 [medline]
PHST- 2023/09/22 00:42 [pubmed]
PHST- 2023/09/21 19:19 [entrez]
PHST- 2023/09/20 00:00 [pmc-release]
AID - S2212-8778(23)00143-6 [pii]
AID - 101809 [pii]
AID - 10.1016/j.molmet.2023.101809 [doi]
PST - ppublish
SO  - Mol Metab. 2023 Dec;78:101809. doi: 10.1016/j.molmet.2023.101809. Epub 2023 Sep 
      20.