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Immunohistochemical characterization of lymphocytes in microscopic colitis
Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Örebro University, School of Medicine, Örebro University, Sweden.ORCID iD: 0000-0001-5460-8888
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Sweden.
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2013 (English)In: Journal of Crohn's and Colitis, ISSN 1197-4982, Vol. 7, no 10, p. e434-e442Article in journal (Refereed) Published
Abstract [en]

Background and Aims: Microscopic colitis (MC), encompassing the subgroups collagenous colitis (CC) and lymphocytic colitis (LC), is characterized by macroscopically normal or near-normal colonic mucosa, and an increased number of intraepithelial lymphocytes (IELs) and mononuclear cell infiltration in the underlying lamina propria (LP), in addition to an increased collagen layer in CC. This study aimed to characterize the inflammatory cells involved in mucosal inflammation, using immunohistochemistry.

Methods Paraffin-embedded biopsies from 23 untreated patients with MC (CC = 13, LC = 10) and 17 controls were stained with antibodies against CD3, CD4, CD8, CD20, CD30, Foxp3, CD45RO and Ki67. Computerized image analysis was used to calculate areas of stained lymphocytes in the surface and crypt epithelia as well as in the LP.

Results In CC and LC, an increase of predominantly CD8+ lymphocytes was seen in both the epithelium and the lamina propria, whereas a decreased amount of CD4+ lymphocytes was found in the lamina propria. CD45RO+ and Foxp3+ cells were more abundant in all areas in both patient groups compared to controls, as were CD20+ areas, although more scarce. Ki67+ areas were only more abundant in the epithelium, whereas CD30+ areas were more abundant in the lamina propria of both patient groups compared to controls.

Conclusions This study confirms an increased amount of CD8+ lymphocytes in the epithelium. Lymphocytic proliferation and activation markers were more abundant, whereas a decreased amount of CD4+ lymphocytes was seen in the LP. Further studies are needed to reveal the underlying mechanism(s).

Place, publisher, year, edition, pages
Elsevier, 2013. Vol. 7, no 10, p. e434-e442
Keyword [en]
Collagenous colitis, Lymphocytic colitis, Microscopic colitis, Lymphocytes, Immunohistochemistry
National Category
Biomedical Laboratory Science/Technology
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-30117DOI: 10.1016/j.crohns.2013.02.007PubMedID: 23523417Scopus ID: 2-s2.0-84884146798OAI: oai:DiVA.org:oru-30117DiVA, id: diva2:638832
Available from: 2013-08-02 Created: 2013-08-02 Last updated: 2018-05-19Bibliographically approved
In thesis
1. Adaptive immune response in the intestinal mucosa of microscopic colitis patients
Open this publication in new window or tab >>Adaptive immune response in the intestinal mucosa of microscopic colitis patients
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Microscopic colitis (MC) is a chronic diarrhoeal disease of unknown aetiology, comprising collagenous colitis (CC) and lymphocytic colitis (LC). The nature of the adaptive local immune responses in the mucosa of MC patients is however far from elucidated. The present study investigates phenotypic and functional characteristics of the adaptive local immune responses in the colonic mucosa of these patients.

Our immunohistochemistry and flow cytometry studies (Paper I & II) demonstrated increased frequencies of CD8+ T cells in the colonic epithelium and lamina propria of both LC and CC patients compared to controls, whereas the frequencies of CD4+ T cells were unaltered or reduced. Our flow cytometry data revealed increased local activation of both CD4+ and CD8+ T cells in the lamina propria as well as the intraepithelial compartment of CC and LC patients compared to controls, demonstrated as increased proportions of these cells expressing the active/memory marker CD45RO and the proliferation marker Ki67.

Analysis of recent thymic emigrants by measuring T cell receptor excision circle (TREC) levels in the colonic mucosa of CC and LC patients revealed reduced TRECs levels in these patients compared to controls (Paper III). These results suggests that the observed increased numbers of T cells in the mucosa of CC and LC patients is due to the expansion of local resident T cells rather than direct recruitment of recent thymic emigrants to the mucosa.

Molecular analysis of T helper (Th) cell and cytotoxic T lymphocyte (Tc) mucosal cytokines at messenger and protein levels in the colonic biopsies from CC and LC patients demonstrated a mixed Th17/Tc17 and Th1/Tc1 mucosal cytokine profile and revealed significant differences in the mucosal cytokine levels in CC and LC patients compared to controls (Paper IV).

Finally, we have set up an in vitro model to investigate how the colonic milieu affects the activation and differentiation of T lymphocytes (Paper V). Our preliminary data indicate increased production of both pro inflammatory and antiinflammatory cytokines by peripheral blood T cells in the presence of soluble factors from the inflamed colonic mucosa of CC patients compared to controls.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2013. p. 83
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 84
Keyword
Microscopic colitis, collagenous colitis, lymphocytic colitis, intraepithelial lymphocytes, lamina propria lymphocytes, T cell receptor excision circle, T helper cells, cytotoxic T lymphocyte and mucosal cytokines
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-27894 (URN)978-91-7668-929-5 (ISBN)
Public defence
2013-05-24, Hörsal P2, Prismahuset, Örebro universitet, Fakultetsgatan 1, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2013-03-18 Created: 2013-03-11 Last updated: 2017-10-17Bibliographically approved

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