Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment.

Sezin Günaltay,Johan Bohr,Nils Nyhlin,Curt Tysk,Olof Hultgren,Elisabeth Hultgren Hörnquist,Ashok Kumar Kumawat

doi:10.1155/2015/132458

Abstract

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 CX3CL1 and the receptors CCR2, CCR3, CCR4, CXCR1, CXCR2, and CX3CR1. 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.

Highlights

Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is characterized clinically by chronic watery diarrhea, abdominal pain, and/or weight loss
LC-HR patients showed similarities with LC patients in terms of enhanced chemokine and receptor expression levels, whereas CC-HR patients had normalized expressions. These results contribute to the knowledge of MC immunopathology, a subtler type of inflammatory bowel disease (IBD)
Increased gene expressions of CXCL9, CXCL10, CXCL11, and CX3CL1 were detected in CC patients compared to both controls and CC-HR

Summary

Introduction

Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is characterized clinically by chronic watery diarrhea, abdominal pain, and/or weight loss. The diagnosis relies on typical histopathological features that are observed upon microscopic examination: lymphocytic infiltration of the epithelium and lamina propria as well as a damaged, flattened, and detached epithelial layer and in CC a characteristic thickened subepithelial collagen layer [1,2,3,4]. Biopsies from both LC and CC patients reveal a mixed inflammatory cell infiltrate in lamina propria, including T and B lymphocytes, plasma cells, eosinophils, neutrophils, mast cells, and macrophages [5,6,7,8,9].

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