Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn’s disease

Abstract

Background: A dominant T helper type 1 (Th1) immune response is thought to be involved in Crohn's disease (CD). SLC/CCL21 and ELC/CCL19, chemokines that regulate T cell homing and promote recirculating T and dendritic cell (DC) interactions, help control antigen specific T cell responses. Aims: To investigate the Th1 response and SLC and ELC in CD pathogenesis. Methods: Surgically resected intestine and mesenteric lymph nodes (MLNs) from controls and patients with CD and ulcerative colitis (UC) were investigated. CD3, CD83, HECA452, VEGFR3, SLC, ELC, and CCR7 expression was studied immunohistochemically. CCR7 mRNA was quantified using real time RT-PCR. Results: ELC was almost undetectable in intestinal samples. SLC was found sporadically in lymphoid follicles, lymphoid aggregate venules, and lymphatic vessels. In MLNs, SLC was highly expressed in high endothelial venules (HEVs), lymphatic vessels, and stromal DCs, predominantly in T cell areas. ELC was highly expressed in mature DCs. There were significantly more SLC positive HEVs and ELC positive mature DCs, important components of T cell areas, in CD. SLC, ELC, and CCR7 mRNA was significantly higher in CD MLNs compared with UC. CD MLNs had increased expression of SLC and ELC, mainly in HEVs, mature DCs, and lymphatic vessels, inducing T cell hyperplasia. CCR7 mRNA was increased in T cell areas. Conclusion:The dominant Th1 immune response is facilitated by interaction of SLC positive HEVs/ lymphatic vessels, ELC positive mature DCs, and CCR7 positive T cells in hyperplastic T cell areas. In CD, memory T cells and mature DCs may home to MLN.

Ectopic lymphoid tissue alters the chemokine gradient, increases lymphocyte retention and exacerbates murine ileitis

“…A significant increase in CCL19 and CCL21 transcripts was observed in tissue from patients with Crohn's ileitis (p<0.05), Crohn's colitis (p<0.05) and ulcerative colitis (p<0.05) (figure 1C,D). Thus, as shown previously,9 increased CCL19 and CCL21 mRNA transcripts were observed in inflamed intestine of patients with IBD.…”

“…The expression of CCL19 and CCL21 is tightly regulated within lymphoid tissues, acting as chemotactic and retentive signals 5–7. CCL21 is also expressed by high endothelial venules (HEV), lymphatics and lymphoid stromal cells8 and overexpressed in a variety of autoimmune diseases 9 10. Recent evidence has highlighted a role for the ectopic expression of lymphoid chemokines CCL19 and CCL21 in the induction of ectopic lymphoid tissue at sites of chronic inflammation 11 12…”

Effect of secondary lymphoid tissue chemokine suppression on experimental ulcerative colitis in mice

“…However, the attraction of DC by CCL21, which is expressed in the lymphoid tissue of the gastrointestinal tract, results in the spread of the bacteria in DCs (Cheminay et al, 2002;Watanabe et al, 2007;Zimmerman et al, 2008;Britschgi et al, 2010;Murphy, 2010;Haessler et al, 2011;Tal et al, 2011). Kawashima et al (2005) analyzed intestinal samples and found that CCL21 was expressed in the intestinal lymph nodes, lymphatic vessels, and the mesenteric lymph nodes. CCL21 was highly expressed in the HEVs, lymphatic vessels, and interstitial DC, especially in the T-cell district.…”

NK cells at the interface between innate and adaptive immunity

“…18 Indeed, in lymph nodes, CCL21 is highly expressed in high endothelial venules (HEVs), lymphatic vessels, and stromal/interdigitating DCs (predominantly in T-cell areas), whereas CCL19 is highly expressed in mature DCs within the T cell zone of para-cortex. 40,41 Accordingly within normal non-inflamed lymph nodes NK cells, which are localized in the para-follicular area next to the para-cortical T-cell area, 42,43 are homogeneously characterized by the CD56 high CD94/NKG2A þ surface phenotype, by low levels of cytolytic activity and by the production of high amounts of interferon (IFN)-g. Thus these cells are very similar to the small CD56 high CD16 À NK cell subset that is found in peripheral blood. The developmental relationship between these two NK cell subsets remains controversial although a recent report demonstrated that upon exposure to interleukin IL2, IL15 or IL12 in vitro peripheral blood CD56 high NK cells gain the typical pattern of CD56 low NK cells.…”