Increased number of mature dendritic cells in Crohn's disease: evidence for a chemokine mediated retention mechanism

Abstract

Our results demonstrate that autocrine and paracrine actions of lymphoid chemokines in Crohn's disease may lead to increased numbers of mature DC away from their usual migration to lymphoid organs and result in the development of a tertiary lymphatic tissue within the bowel wall maintaining the autoimmune inflammation in Crohn's disease.

CD83+CCR7− Dendritic Cells Accumulate in the Subepithelial Dome and Internalize Translocated Escherichia coli HB101 in the Peyer's Patches of Ileal Crohn's Disease

“…In addition, the expression of CCL21 by reticular cells and lymphatic vessels facilitated the entrapment of the DCs in the IFR and lymph nodes of CD tissues. 29 In our present study, however, most of the accumulated CD83…”

“…A similar observation, with accumulation of mature CD83 ϩ DCs, was previously found in the colonic mucosa of CD patients. 29 However, they found that the majority of the CD83 ϩ DCs were CCR7 ϩ , maybe as a result of examining the entire intestinal wall. In addition, the expression of CCL21 by reticular cells and lymphatic vessels facilitated the entrapment of the DCs in the IFR and lymph nodes of CD tissues.…”

Dendritic Cells in the Kidney

“…It is unclear, however, the degree to which environmental cues that are unique to the kidney (e.g., Tolllike receptor recognition of the kidneyrestricted protein, Tamm-Horsfall glycoprotein 90 ) "imprint" rDC to polarize preferentially naive T lymphocytes and generate kidney-tropic Th effectors. 91 Moreover, little is known regarding environmental cues that may retard the egress of mature, antigen-presenting rDC out of the kidney (as recently shown in the bowel 92 ), a recipe for inducing adaptive immune responses within the kidney itself and subsequently organizing pathogenic "nephron-associated lymphoid tissue. "…”

CCL21 Expression Pattern of Human Secondary Lymphoid Organ Stroma Is Conserved in Inflammatory Lesions with Lymphoid Neogenesis

“…It is thus unclear whether and to what extent inflammation influences the pattern of CCL21 expression in ELTs or whether the same cellular sources are responsible for CCL21 production in SLOs and ELTs. 5,13,14 Although CCL21 is constitutively expressed in murine SLOs by T-zone stromal cells, 15 lymphatic vessels, and HEVs 16 as an expression of a species-specific difference, we and others have recently demonstrated that human SLO HEVs lack CCL21 mRNA. 10,17 Instead, the chemokine is produced by lymphatics and nonendothelial cells (non-ECs) within the T area, 17 and translocation of the protein through HEVs has been surmised to mediate T-cell homing, 17 in keeping with the process of transcytosis previously demonstrated for CCL19.…”