Regulation and Role of αE Integrin and Gut Homing Integrins in Migration and Retention of Intestinal Lymphocytes during Inflammatory Bowel Disease

Mary E. Keir, Franklin Fuh, Ryan Ichikawa, Meghan Acres, Jason A. Hackney, Gillian Hulme, Christopher D. Carey, Jeremy Palmer, Claire J. Jones, Anna K. Long, Jenny Jiang, Sha Klabunde, John C. Mansfield, Cary M. Looney, William A. Faubion, Andrew Filby, John A. Kirby, Jacqueline McBride, Christopher A. Lamb

Research output: Contribution to journalArticlepeer-review


Targeting interactions between α4β7 integrin and endothelial adhesion molecule MAdCAM-1 to inhibit lymphocyte migration to the gastrointestinal tract is an effective therapy in inflammatory bowel disease (IBD). Following lymphocyte entry into the mucosa, a subset of these cells expresses αEβ7 integrin, which is expressed on proinflammatory lymphocytes, to increase cell retention. The factors governing lymphocyte migration into the intestinal mucosa and αE integrin expression in healthy subjects and IBD patients remain incompletely understood. We evaluated changes in factors involved in lymphocyte migration and differentiation within tissues. Both ileal and colonic tissue from active IBD patients showed upregulation of ICAM-1, VCAM-1, and MAdCAM-1 at the gene and protein levels compared with healthy subjects and/or inactive IBD patients. β1 and β7 integrin expression on circulating lymphocytes was similar across groups. TGF-β1 treatment induced expression of αE on both β7+ and β72 T cells, suggesting that cells entering the mucosa independently of MAdCAM-1/α4β7 can become αEβ7+. ITGAE gene polymorphisms did not alter protein induction following TGF-β1 stimulation. Increased phospho-SMAD3, which is directly downstream of TGF-β, and increased TGF-β-responsive gene expression were observed in the colonic mucosa of IBD patients. Finally, in vitro stimulation experiments showed that baseline β7 expression had little effect on cytokine, chemokine, transcription factor, and effector molecule gene expression in αE+ and αE2 T cells. These findings suggest cell migration to the gut mucosa may be altered in IBD and α4β72, and α4β7+ T cells may upregulate αEβ7 in response to TGF-β once within the gut mucosa.

Original languageEnglish (US)
Pages (from-to)2245-2254
Number of pages10
JournalJournal of Immunology
Issue number9
StatePublished - Nov 1 2021

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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