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      Different distribution of mucosal-associated invariant T cells within the human cecum and colon

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          Abstract

          Introduction

          Mucosal-associated invariant T (MAIT) cells are innate-like T cells that are involved in anti-bacterial immunity. MAIT cells are found in the intestines, but their role and distribution within the large intestine have not been fully elucidated. Therefore, we investigated the distribution of MAIT cells within the cecum and colon.

          Material and methods

          Surgically resected tissues of the cecum and colon were obtained from 4 patients with cecal appendix cancer and 8 patients with colorectal cancer, respectively. Lymphocytes were isolated from the intestinal epithelium (intraepithelial lymphocytes – IELs) and the underlying lamina propria (lamina propria lymphocytes – LPLs), and then, MAIT cells were analyzed by flow cytometry.

          Results

          Compared with the colon, the cecum showed a significantly increased frequency of MAIT cells among IELs (p < 0.01). CD69 expression on MAIT cells was significantly increased in the cecum and colon compared with that in the blood, and the frequency of natural killer group 2, member A + cells among MAIT cells was significantly increased in the cecum.

          Conclusions

          These results suggest that the distribution of MAIT cells was different between the cecum and colon and that MAIT cells were more likely to be activated, especially in the intestinal epithelium of the cecum than in the colon and blood.

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          Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments.

          Ilona Kryczek, Mousumi Banerjee, Pui Cheng … (2009)
          Th17 cells play an active role in autoimmune diseases. However, the nature of Th17 cells is poorly understood in cancer patients. We studied Th17 cells, the associated mechanisms, and clinical significance in 201 ovarian cancer patients. Tumor-infiltrating Th17 cells exhibit a polyfunctional effector T-cell phenotype, are positively associated with effector cells, and are negatively associated with tumor-infiltrating regulatory T cells. Tumor-associated macrophages promote Th17 cells through interleukin-1beta (IL-1beta), whereas tumor-infiltrating regulatory T cells inhibit Th17 cells through an adenosinergic pathway. Furthermore, through synergistic action between IL-17 and interferon-gamma, Th17 cells stimulate CXCL9 and CXCL10 production to recruit effector T cells to the tumor microenvironment. The levels of CXCL9 and CXCL10 are associated with tumor-infiltrating effector T cells. The levels of tumor-infiltrating Th17 cells and the levels of ascites IL-17 are reduced in more advanced diseases and positively predict patient outcome. Altogether, Th17 cells may contribute to protective human tumor immunity through inducing Th1-type chemokines and recruiting effector cells to the tumor microenvironment. Inhibition of Th17 cells represents a novel immune evasion mechanism. This study thus provides scientific and clinical rationale for developing novel immune-boosting strategies based on promoting the Th17 cell population in cancer patients.
          Article 0 comments Cited 245 times – based on 0 reviews     Review now
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            Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells.

            Emily Fleming, Hannah Tharmalingham, Natasha Sahgal … (2012)
            Human mucosal associated invariant T (MAIT) CD8(+) and Tc17 cells are important tissue-homing cell populations, characterized by high expression of CD161 ((++)) and type-17 differentiation, but their origins and relationships remain poorly defined. By transcriptional and functional analyses, we demonstrate that a pool of polyclonal, precommitted type-17 CD161(++)CD8αβ(+) T cells exist in cord blood, from which a prominent MAIT cell (TCR Vα7.2(+)) population emerges post-natally. During this expansion, CD8αα T cells appear exclusively within a CD161(++)CD8(+)/MAIT subset, sharing cytokine production, chemokine-receptor expression, TCR-usage, and transcriptional profiles with their CD161(++)CD8αβ(+) counterparts. Our data demonstrate the origin and differentiation pathway of MAIT-cells from a naive type-17 precommitted CD161(++)CD8(+) T-cell pool and the distinct phenotype and function of CD8αα cells in man.
            Article 0 comments Cited 124 times – based on 0 reviews     Review now
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              Recent advances in inflammatory bowel disease: mucosal immune cells in intestinal inflammation.

              Arthur Kaser, M. Cader (2013)
              The intestine and its immune system have evolved to meet the extraordinary task of maintaining tolerance to the largest, most complex and diverse microbial commensal habitat, while meticulously attacking and containing even minute numbers of occasionally incoming pathogens. While our understanding is still far from complete, recent studies have provided exciting novel insights into the complex interplay of the many distinct intestinal immune cell types as well as the discovery of entirely new cell subsets. These studies have also revealed how proper development and function of the intestinal immune system is dependent on its specific microbiota, which appears to have evolutionarily co-evolved. Here we review key immune cells that maintain intestinal homeostasis and, conversely, describe how altered function and imbalances may lead to inflammatory bowel disease (IBD). We highlight the latest developments within this field, covering the major players in IBD including intestinal epithelial cells, macrophages, dendritic cells, adaptive immune cells, and the newly discovered innate lymphoid cells, which appear of characteristic importance for immune function at mucosal surfaces. We set these mucosal immune pathways in the functional context of IBD risk genes where such insight is available. Moreover, we frame our discussion of fundamental biological pathways that have been elucidated in model systems in the context of results from clinical trials in IBD that targeted key mediators secreted by these cells, as an attempt of 'functional' appraisal of these pathways in human disease.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cent Eur J Immunol
                Journal ID (iso-abbrev): Cent Eur J Immunol
                Journal ID (publisher-id): CEJI
                Title: Central-European Journal of Immunology
                Publisher: Polish Society of Experimental and Clinical Immunology
                ISSN (Print): 1426-3912
                ISSN (Electronic): 1644-4124
                Publication date (Electronic): 15 April 2019
                Publication date (Print): 2019
                Volume: 44
                Issue: 1
                Pages: 75-83
                Affiliations
                Graduate School of Medical and Dental Sciences, Niigata University, Japan
                Author notes
                Correspondence: Satoshi Yamagiwa, MD, PhD, Graduate School of Medical and Dental Sciences, Niigata University, Japan. e-mail: syamagi@ 123456med.niigata-u.ac.jp
                Article
                Publisher ID: 84020
                DOI: 10.5114/ceji.2019.84020
                PMC ID: 6526592
                SO-VID: afa8b845-eb9c-46c6-a8b8-4d2524a6b35c
                Copyright © Copyright: © 2019 Polish Society of Experimental and Clinical Immunology
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

                History
                Date received : 05 September 2017
                Date accepted : 02 February 2018
                Categories
                Subject: Clinical Immunology

                Keywords: mucosal-associated invariant t cells,cecum,colon,intraepithelial lymphocytes,lamina propria lymphocytes
                Data availability:
                Keywords: mucosal-associated invariant t cells, cecum, colon, intraepithelial lymphocytes, lamina propria lymphocytes

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