Increased expression of DC‐SIGN⁺IL‐12⁺IL‐18⁺ and CD83⁺IL‐12^–IL‐18^– dendritic cell populations in the colonic mucosa of patients with Crohn's disease

Abstract

Dentritic cells (DC) as antigen-presenting cells are most likely responsible for regulation of abnormal T cell activation in Crohn's disease (CD), a chronic inflammatory bowel disease. We have analyzed the expression of activation and maturation markers on DC in the colon mucosa from patients with CD compared with normal colon, using immunohistochemical techniques. We found two distinct populations of DC present in CD patients: a DC-specific ICAM-3 grabbing non-integrin (DC-SIGN) + population that was present scattered throughout the mucosa, and a CD83 + population that was present in aggregated lymphoid nodules and as single cells in the lamina propria. In normal colon the number of DC-SIGN + DC was lower and CD83 + DC were detected only in very few solitary lymphoid nodules. Co-expression of activation markers and cytokine synthesis was analyzed with three-color confocal laser scanning microscopy analysis. CD80 expression was enhanced on the majority of DC-SIGN + DC in CD patients, whereas only a proportion of the CD83 + DC co-expressed CD80 in CD as well as in normal tissue. Surprisingly, IL-12 and IL-18 were only detected in DC-SIGN + DC and not in CD83 + DC. A similar pattern of cytokine production was observed in normal colon albeit to a much lesser extent. The characteristics of these in-situ-differentiated DC markedly differ from the in-vitro-generated DC that simultaneously express DC-SIGN, CD83 and cytokines.

Glycosylation-Dependent Interactions of C-Type Lectin DC-SIGN with Colorectal Tumor-Associated Lewis Glycans Impair the Function and Differentiation of Monocyte-Derived Dendritic Cells

“…In addition, tumors use a variety of mechanisms to evade detection and elimination by the immune system (19,23). Maturation of DCs is crucial for their ability to induce adaptive immunity.…”

“…8A), suggesting that the increased expression of DC-SIGN ligands on colorectal cancer cells, in addition to the altered glycosylation that results in increased levels of Le a and Le b glycans on colorectal cancer cells, may promote interactions with DC-SIGN. It has been reported that DC-SIGN-positive cells are detected not only within the mucosa of normal colon tissue but also within cancer colon tissue (14,19). Next, to determine whether DC-SIGN-positive cells may interact with primary colorectal cancer cells in situ, we analyzed the interaction of endogenous DC-SIGN with Le a glycan in cancer colon tissue.…”

Role of mucosal dendritic cells in inflammatory bowel disease

“…In addition the presence of CD83 + and DC -SIGN + DCs was described [19] . Human and mouse mucosal DCs are assumed to be less responsive to microbial-derived TLR-lig ands compared to spleen or blood born DCs [17] Despite the functional subspecifications of DCs, DCs are characterized by a remarkable plasticity between DCs which is influenced by the local environment, the antigen itself or the activation state of the DC [9,20] .…”

“…In inflamed tissues DCs are matured and increased in 5142 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol Volume 14 Number 33 numbers. The CD83 -CD80 + DCSIGN + DC subsets produce the cytokine IL-12 and IL-18, which promote TH1 development [19] . Also, in the peripheral blood and in the lamina propria of patients with CD or UC the numbers of CD86 + CD40 + DCs are increased.…”

Intestinal dendritic cell and macrophage subsets: Tipping the balance to Crohn's Disease?

“…This is likely due to difficulties in obtaining large enough samples from the relevant tissues to identify these scarce cells. However, studies using immunohistochemistry have been performed on biopsies from the colon of normal individuals and Crohn's Disease patients and showed the presence of different subsets of phagocytes in human colon [27][28][29][30]. Information obtained from immunohistochemical stainings is invaluable since they also show the location of the cells within the tissue.…”