Clinical-alimentary tractCD40-mediated immune-nonimmune cell interactions induce mucosal fibroblast chemokines leading to T-Cell transmigration☆
Section snippets
Isolation and cultures of HIF and HIMEC
Surgical specimens used for isolation of HIF and HIMEC were all of colonic origin. Mucosal strips were obtained from histologically normal tissue of patients admitted for bowel resection due to malignant and nonmalignant conditions, including colon cancer, benign polyps, and diverticulosis, or tissue involved by CD or UC. All diagnoses were confirmed by clinical, radiologic, endoscopic, and histologic criteria. Isolation of HIF and HIMEC was performed as previously reported.31, 32 Briefly, HIF
Expression of CD40 and CD40L in normal and IBD-involved colonic mucosa
Immunohistochemistry for CD40 of histologically normal colonic tissue from control subjects showed staining of some mononuclear cells in the lamina propria and weak staining of microvascular endothelial cells in the submucosa (Figure 1A). Muscularis mucosae and mesenchymal cells were negative for CD40. In actively inflamed CD tissue, there was strong and diffuse CD40 staining of mononuclear, endothelial, and mesenchymal cells in the mucosa and submucosa (Figure 1B), and the same cells were
Discussion
The results of this study show that the cognate interaction of mucosal CD40-positive nonimmune cells with CD40L-positive T cells results in the up-regulation of CAM by HIF, which increase their T-cell binding capacity and secretion of biologically active chemoattractants able to induce migration of T cells through a HIMEC monolayer. This series of events is likely to recapitulate what occurs in vivo given the enhanced expression of CD40 and CD40L by nonimmune and immune cells, respectively, in
Acknowledgements
The authors thank the Human Tissue Procurement Facility of University Hospitals of Cleveland (Cleveland, OH) for supplying tissue samples and Immunex Corp. (Seattle, WA) for providing essential reagents.
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2021, Pharmacology and TherapeuticsCitation Excerpt :sCD40L stimulates lung fibroblast activation, as evidenced by production of IL-6 and IL-8 (Sempowski, Chess, & Phipps, 1997). Ligation of CD40 on human intestinal fibroblasts by CD40L-bearing T cells or sCD40L, increases their T-cell binding capacity and promotes T cell migration through endothelial monolayers by upregulating ICAM-1 and VCAM-1 expression as well as interleukin-8 and RANTES production (Vogel, West, et al., 2004). CD40 ligation by CD40L enhances ICAM-1 and IL-8 expression in IFN-γ stimulated keratinocytes (Denfeld, Hollenbaugh, et al., 1996).
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2019, BloodCitation Excerpt :Tissues were obtained from histologically normal, noninflamed large-bowel specimens (non-IBD controls) from patients admitted for bowel resection because of conditions that included colon cancer, benign polyps, diverticulitis, and colonic inertia. HIMECs were isolated and cultured as previously reported.30,31 The study was approved by the Institutional Review Board of the Cleveland Clinic.
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Supported by grants from the National Institutes of Health (NRSA DK10041 to J.D.V., DK30399 and DK50984 to C.F., and DK58867 to S.A.S).