Christopher J Tyler1,2, Mauricio Guzman1,2, Luke R Lundborg1,2, Shaila Yeasmin1,2, Tamara Perez-Jeldres3,4, Andres Yarur5, Brian Behm6, Parambir S Dulai2, Derek Patel2, Giorgos Bamias7, Jesús Rivera-Nieves1,2. 1. Inflammatory Bowel Disease Center, Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA. 2. San Diego VA Medical Center, San Diego, CA, USA. 3. Universidad Católica de Chile, Santiago, Chile. 4. Hospital San Borja Arriarán, Santiago, Chile. 5. Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, WI, USA. 6. Division of Gastroenterology, University of Virginia, Charlottesville, VI, USA. 7. GI Unit, 3rd Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece.
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.
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.
Authors: Ignacio Catalan-Serra; Arne Kristian Sandvik; Torunn Bruland; Juan Carlos Andreu-Ballester Journal: J Crohns Colitis Date: 2017-09-01 Impact factor: 9.071
Authors: S Hosomi; N Oshitani; N Kamata; M Sogawa; H Okazaki; T Tanigawa; H Yamagami; K Watanabe; K Tominaga; T Watanabe; Y Fujiwara; K Maeda; K Hirakawa; T Arakawa Journal: Clin Exp Immunol Date: 2010-11-19 Impact factor: 4.330
Authors: Nicole J Tarlton; Caroline M Green; Nicole H Lazarus; Lusijah Rott; Anthony P Wong; Oren N Abramson; Martina Bremer; Eugene C Butcher; Tzvia Abramson Journal: Inflamm Bowel Dis Date: 2012-04-05 Impact factor: 5.325
Authors: D Elewaut; N Van Damme; F De Keyser; D Baeten; P De Paepe; H Van Vlierberghe; H Mielants; C Cuvelier; G Verbruggen; E M Veys; M De Vos Journal: Acta Gastroenterol Belg Date: 1998 Jul-Sep Impact factor: 1.316
Authors: J R Fergusson; M H Hühn; L Swadling; L J Walker; A Kurioka; A Llibre; A Bertoletti; G Holländer; E W Newell; M M Davis; E Sverremark-Ekström; F Powrie; S Capone; A Folgori; E Barnes; C B Willberg; J E Ussher; P Klenerman Journal: Mucosal Immunol Date: 2015-07-29 Impact factor: 7.313
Authors: Britt Roosenboom; Peter J Wahab; Carolijn Smids; Marcel J M Groenen; Elly van Koolwijk; Ellen G van Lochem; Carmen S Horjus Talabur Horje Journal: Inflamm Bowel Dis Date: 2019-08-20 Impact factor: 5.325
Authors: Hao Chen; Mai Chan Lau; Michael Thomas Wong; Evan W Newell; Michael Poidinger; Jinmiao Chen Journal: PLoS Comput Biol Date: 2016-09-23 Impact factor: 4.475