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Inherent Immune Cell Variation Within Colonic Segments Presents Challenges for Clinical Trial Design. J Crohns Colitis 2020 Oct 05;14(10):1364-1377

Date

04/03/2020

Pubmed ID

32239151

Pubmed Central ID

PMC7533898

DOI

10.1093/ecco-jcc/jjaa067

Scopus ID

2-s2.0-85092680131   1 Citation

Abstract

BACKGROUND AND AIMS: Intestinal biopsy sampling during IBD trials represents a valuable adjunct strategy for understanding drug responses at the tissue level. Given the length and distinctive embryonic origins of the proximal and distal colon, we investigated whether inherent regional differences of immune cell composition could introduce confounders when sampling different disease stages, or pre/post drug administration. Here, we capitalise on novel mass cytometry technology to perform deep immunophenotyping of distinct healthy colonic segments, using the limited numbers of biopsies that can be harvested from patients.

METHODS: Biopsies [2.8 mm] were collected from the caecum, transverse colon, descending colon, and rectum of normal volunteers. Intestinal leukocytes were isolated, stained with a panel of 37 antibodies, and mass cytometry data acquired.

RESULTS: Site-specific patterns of leukocyte localisation were observed. The proximal colon featured increased CD8+ T cells [particularly resident memory], monocytes, and CD19+ B cells. Conversely, the distal colon and rectum tissues exhibited enrichment for CD4+ T cells and antibody-secreting cells. The transverse colon displayed increased abundance of both γδ T cells and NK cells. Subsets of leukocyte lineages also displayed gradients of expression along the colon length.

CONCLUSIONS: Our results show an inherent regional immune cell variation within colonic segments, indicating that regional mucosal signatures must be considered when assessing disease stages or the prospective effects of trial drugs on leukocyte subsets. Precise protocols for intestinal sampling must be implemented to allow for the proper interpretation of potential differences observed within leukocyte lineages present in the colonic lamina propria.

Author List

Tyler CJ, Guzman M, Lundborg LR, Yeasmin S, Perez-Jeldres T, Yarur A, Behm B, Dulai PS, Patel D, Bamias G, Rivera-Nieves J

Author

Andres Jose Yarur MD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Antigens, CD19
B-Lymphocytes
Biopsy
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Clinical Trials as Topic
Female
Humans
Immunity, Cellular
Inflammatory Bowel Diseases
Intestinal Mucosa
Male
Monocytes
Patient Acuity
Patient Selection