Inherent Immune Cell Variation Within Colonic Segments Presents Challenges for Clinical Trial Design

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dc.contributor.authorTyler, Christopher J.
dc.contributor.authorGuzman, Mauricio
dc.contributor.authorLundborg, Luke R.
dc.contributor.authorYeasmin, Shaila
dc.contributor.authorPerez-Jeldres, Tamara
dc.contributor.authorYarur, Andres
dc.contributor.authorBehm, Brian
dc.contributor.authorDulai, Parambir S.
dc.contributor.authorPatel, Derek
dc.contributor.authorBamias, Giorgos
dc.contributor.authorRivera-Nieves, Jesus
dc.date.accessioned2025-01-23T19:47:06Z
dc.date.available2025-01-23T19:47:06Z
dc.date.issued2020
dc.description.abstractBackground 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.
dc.description.abstractMethods: 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.
dc.description.abstractResults: Site-specific patterns of leukocyte localisation were observed. The proximal colon featured increased CD8* 1 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 gamma delta T cells and NK cells. Subsets of leukocyte lineages also displayed gradients of expression along the colon length.
dc.description.abstractConclusions: 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.
dc.fuente.origenWOS
dc.identifier.doi10.1093/ecco-jcc/jjaa067
dc.identifier.eissn1876-4479
dc.identifier.issn1873-9946
dc.identifier.urihttps://doi.org/10.1093/ecco-jcc/jjaa067
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100348
dc.identifier.wosidWOS:000593067100005
dc.issue.numero10
dc.language.isoen
dc.pagina.final1377
dc.pagina.inicio1364
dc.revistaJournal of crohns & colitis
dc.rightsacceso restringido
dc.subjectmass cytometry
dc.subjectlamina propria
dc.subjectrandomised controlled trials
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleInherent Immune Cell Variation Within Colonic Segments Presents Challenges for Clinical Trial Design
dc.typeartículo
dc.volumen14
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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