Distinct immune characteristics distinguish hereditary and idiopathic chronic pancreatitis

Bomi Lee, Julia Z. Adamska, Hong Namkoong, Melena D. Bellin, Josh Wilhelm, Gregory L. Szot, David M. Louis, Mark M. Davis, Stephen J. Pandol, Aida Habtezion

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Chronic pancreatitis (CP) is considered an irreversible fibroinflammatory pancreatic disease. Despite numerous animal model studies, questions remain about local immune characteristics in human CP. We profiled pancreatic immune cell characteristics in control organ donors and CP patients including those with hereditary and idiopathic CP undergoing total pancreatectomy with islet autotransplantation. Flow cytometric analysis revealed a significant increase in the frequency of CD68+ macrophages in idiopathic CP. In contrast, hereditary CP samples showed a significant increase in CD3+ T cell frequency, which prompted us to investigate the T cell receptor β (TCRβ) repertoire in the CP and control groups. TCRβ sequencing revealed a significant increase in TCRβ repertoire diversity and reduced clonality in both CP groups versus controls. Interestingly, we observed differences in Vβ-Jβ gene family usage between hereditary and idiopathic CP and a positive correlation of TCRβ rearrangements with disease severity scores. Immunophenotyping analyses in hereditary and idiopathic CP pancreases indicate differences in innate and adaptive immune responses, which highlights differences in immunopathogenic mechanisms of disease among subtypes of CP. TCR repertoire analysis further suggests a role for specific T cell responses in hereditary versus idiopathic CP pathogenesis, providing insights into immune responses associated with human CP.

Original languageEnglish (US)
Pages (from-to)2705-2711
Number of pages7
JournalJournal of Clinical Investigation
Volume130
Issue number5
DOIs
StatePublished - May 1 2020

Bibliographical note

Funding Information:
This study was supported in part by NIH grant DK105263 (to AH), a National Pancreas Foundation (NPF) 2019 Research Grant (BL), and the HHMI (MMD, DML). We thank our collaborators, patients, and donors for providing precious human pancreas tissues and the Habtezion laboratory members for their helpful comments.

Publisher Copyright:
Copyright: © 2020, American Society for Clinical Investigation.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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