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

• DOI: 10.4049/jimmunol.2100220
• Publication Date: 2021-09-24T17:10:26Z
• Authors: 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
• Keywords: Homing (biology)

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