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Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment
Örebro universitet, Institutionen för hälsovetenskap och medicin.ORCID-id: 0000-0002-9635-0341
Örebro universitet, Institutionen för hälsovetenskap och medicin. Institute of Infection, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom.ORCID-id: 0000-0002-2244-9816
Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län.ORCID-id: 0000-0002-0942-0816
Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län.
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2015 (Engelska)Ingår i: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, artikel-id 132458Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhea. Various immune cell infiltrations in the epithelium and lamina propria are seen in MC immunopathology. We compared gene and protein expressions of different immune cell attracting chemokines and their receptors in colon biopsies from MC patients in active disease or histopathological remission (CC/LC-HR) with controls, using qRT-PCR and Luminex, respectively. CC and LC patients with active disease demonstrated a mixed chemokine profile with significantly enhanced gene and/or protein expressions of the chemokines CCL2, CCL3, CCL4, CCL5, CCL7, CCL22, CXCL8, CXCL9, CXCL10, CXCL11, and CX(3)CL1 and the receptors CCR2, CCR3, CCR4, CXCR1, CXCR2, and CX(3)CR1. Enhanced chemokine/chemokine receptor gene and protein levels in LC-HR patients were similar to LC patients, whereas CC-HR patients demonstrated almost normalized levels. These findings expand the current understanding of the involvement of various immune cells in MC immunopathology and endorse chemokines as potential diagnostic markers as well as therapeutic candidates. Moreover, this study further supports the hypothesis that CC and LC are two different entities due to differences in their immunoregulatory responses.

Ort, förlag, år, upplaga, sidor
2015. artikel-id 132458
Nationell ämneskategori
Cell- och molekylärbiologi Immunologi inom det medicinska området
Forskningsämne
Immunologi
Identifikatorer
URN: urn:nbn:se:oru:diva-44605DOI: 10.1155/2015/132458ISI: 000353128700001Scopus ID: 2-s2.0-84928473938OAI: oai:DiVA.org:oru-44605DiVA, id: diva2:811426
Anmärkning

Funding Agencies:

Örebro University Hospital Research Foundation (Nyckelfonden)

Research Committee, Orebro County Council

Örebro University

Tillgänglig från: 2015-05-12 Skapad: 2015-05-12 Senast uppdaterad: 2018-06-30Bibliografiskt granskad
Ingår i avhandling
1. Dysregulated mucosal immune responses in microscopic colitis patients
Öppna denna publikation i ny flik eller fönster >>Dysregulated mucosal immune responses in microscopic colitis patients
2016 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC) is a common cause of chronic watery diarrhea. The diagnosis relies on typical histopathological changes observed upon microscopic examination. The studies in this thesis investigated innate and adaptive immune responses in the colonic mucosa of MC patients, also comparing patients with active disease (CC and LC) and histopathologically in remission (CC/LC-HR). We first analyzed expression of interleukin-1/Toll-like receptor (IL-1/TLR) signaling regulators in MC patients (Paper I). Our results showed enhanced IRAK-M, microRNA-146a, -155 and -21 expressions, whereas IL-37 gene expression was reduced in CC and LC patients as compared to non-inflamed controls. These results suggest different pathophysiological mechanisms in MC patients. The mixed inflammatory cell infiltrations seen in the lamina propria of MC patients might be a result of dysregulated expression of chemotactic mediators. In Paper II, we showed that MC patients display mainly an increased expression of chemokines and chemokine receptors in active disease as compared to noninflamed controls. In Paper III, we examined if the decreased IL-37 expression seen in Paper I could mediate the upregulation of chemokines seen in Paper II. We showed that a relatively small reduction in the ability of epithelial cells to produce IL-37 results in mainly increased chemokine expressions in a pattern similar to the findings in Paper II. In order to understand the nature of infiltrating T cells commonly observed in MC patients, we analyzed the T cell receptor (TCR) β chains in colonic biopsies of MC patients (Paper IV). Our results showed significant differences in TCRβ repertoire, which suggests selectively expanded T cell clones in active MC and histopathologically in remission patients. Altogether, these results i) increase the knowledge of MC pathogenesis by showing changes in TLR signaling regulators, enhanced chemokine and their receptor expressions involved in a mixed immune cell infiltrations and selectively expanded T cell clones in CC and LC patients, as well as in histopathological remission ii) might potentially increase the possibility of more target-specific therapies based on IL-37 induction, chemokines or chemokine receptor inhibitions, or hindering T cell infiltration according to TCR clonality.

Ort, förlag, år, upplaga, sidor
Örebro: Örebro university, 2016. s. 102
Serie
Örebro Studies in Medicine, ISSN 1652-4063 ; 132
Nyckelord
Microscopic colitis, collagenous colitis, lymphocytic colitis, TLR, chemokine, chemokine receptor, IL-37, TCR
Nationell ämneskategori
Immunologi inom det medicinska området Annan medicinsk grundvetenskap
Forskningsämne
Immunologi; Biomedicin
Identifikatorer
urn:nbn:se:oru:diva-47390 (URN)978-91-7529-118-5 (ISBN)
Disputation
2016-03-04, Campus USÖ, Örebro universitet, hörsal C2, Södra Grev Rosengatan, Örebro, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2016-01-13 Skapad: 2016-01-13 Senast uppdaterad: 2018-01-10Bibliografiskt granskad

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Gunaltay, SezinKumawat, Ashok KumarNyhlin, NilsBohr, JohanTysk, CurtHultgren, OlofHultgren-Hörnquist, Elisabeth

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Gunaltay, SezinKumawat, Ashok KumarNyhlin, NilsBohr, JohanTysk, CurtHultgren, OlofHultgren-Hörnquist, Elisabeth
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Institutionen för hälsovetenskap och medicinRegion Örebro länInstitutionen för läkarutbildning
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Mediators of Inflammation
Cell- och molekylärbiologiImmunologi inom det medicinska området

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