W13 - Vedolizumab Reduces Dendritic Cells and Naïve Lymphocytes in the Colon Mucosa

Wednesday, June 22, 2022

6:15 PM – 7:30 PM PT

Presenting Author(s)

JL

James D. Lord, MD, PhD

Assistant Research Member
Benaroya Research Institute
SEATTLE, Washington, United States

Co-Author(s)

RK

Ramya Kongala, n/a

Technician II
Benaroya Research Institute
Seattle, Washington, United States
JJ

Julius Juarez, PhD

Scientist
Takeda
Cambridge, Massachusetts, United States

Vedolizumab blocks integrin alpha4/beta7 interaction with MAdCAM-1 on intestinal vascular endothelial cells. It is believed to treat inflammatory bowel disease (IBD) by preventing alpha4/beta7+ cells in blood from entering the intestinal mucosa. By CyTOF and flow cytometry, we found high expression of alph4/beta7 on nearly all myeloid dendritic cells in the blood. Flow cytometry was also performed on colon biopsies from 71 IBD patients on vedolizumab matched 1:1 with similar biopsies from 71 matched IBD patients not on vedolizumab. In the colon, vedolizumab use was associated with significantly fewer intramucosal myeloid dendritic cells (CD1c+, CD14-, CD11c+, HLA-DR+, Wilcoxon p=0.000001) in patients responsive to vedolizumab, but not in non-responders, relative to their respective controls. Fewer intramucosal naïve B (IgD+, Wilcoxon p=0.0001) and CD4 T cells (CD45RA+, Wilcoxon p=0.001) were also observed, regardless of treatment efficacy. No differences were observed in the frequency of other T or B cell subsets, including CD8 T cells, effector T cells, plasma cells and memory B cells expressing different immunoglobin isotypes, suggesting that they have an alternative means of recruitment not present among naïve lymphocytes, such as integrin alpha4/beta1, which binds VCAM-1. Thus we find no evidence that that vedolizumab functions by preventing effector lymphocytes from entering the intestinal mucosa. We instead associated vedolizumab use with fewer colonic naïve lymphocyte and myeloid dendritic cells. The latter is of particular interest, as it alone correlates with clinical response to this therapy.