Corticotropin-releasing Factor Changes the Phenotype and Function of Dendritic Cells in Mouse Mesenteric Lymph Nodes

Abstract

Background/AimsDendritic cells (DCs) are a significant contributor to the pathology of numerous chronic inflammatory autoimmune disorders; however, the effects of Corticotropin-releasing factor (CRF) on intestinal DCs are poorly understood. In this study, we investigated the role of CRF in alterations of intestinal dendritic cell phenotype and function. MethodsMouse mesenteric lymph node dendritic cells (MLNDCs) were obtained using magnetic bead sorting. Surface expression of CRF receptor type 1 (CRF-R1) and CRF-R2 was determined by double-labeling immunofluorescence and quantitative polymerase chain reaction (qPCR) and MLNDCs were subsequently exposed to CRF in the presence or absence of CRF-R1 and CRF-R2 antagonists. Expression of surface molecules (MHC-I and MHC-II) and co-stimulatory molecules (CD80 and CD86) was determined by flow cytometric and western blot analyses, and the T cell stimulatory capacity of MLNDCs was evaluated by mixed lymphocyte reaction. ResultsImmunofluorescent staining and quatitative polymerase chain reaction indicated that both the CRF receptors (CRF-R1 and CRF-2) are expressed on the surface of MLNDCs. Exposure to CRF increased the expression of MHC-II on MLNDCs as well as their capacity to stimulate T cell proliferation. MLNDCs treated with CRF-R1 antagonist exhibited a phenotype characterized by a less activated state and reduced surface expression of MHC-II, and consequently showed reduced capacity to stimulate T cells. In contrast, treatment of MLNDCs with CRF-R2 antagonist yielded an opposite result. Conclusions

Corticotropin-Releasing Hormone Receptor Alters the Tumor Development and Growth in Apcmin/+ Mice and in a Chemically-Induced Model of Colon Cancer

“…CRH-induced glucocorticoids mitigate the stress response by suppressing the endocrine activity of the hypothalamus and the pituitary gland [4]. Given the ability of glucocorticoids to suppress inflammation and immune responses, the CRH family peptides additionally regulate the inflammation and immune responses at peripheral organs [5,6]. The CRH family peptides include CRH [7], urocortin I (UCN I) [8], UCN II (stresscopin-related peptide) [9], and UCN III (stresscopin) [10].…”

Chronic Stress, Inflammation, and Colon Cancer: A CRH System-Driven Molecular Crosstalk

“…Peripheral CRH targets intestinal lamina propria dendritic cells whichexpress both CRH receptors [17,113,134]. Intestinal dendritic cells, as components of the adaptive immunity, internalize luminal antigens, through endocytosis, and present them to naïve T cells located in mesenteric lymph nodes [17].…”

“…Previous studies have reported implication of the intestinal dendritic cells in the pathogenesis of IBD, based on their CRH-producing and secreting abilities upon bacterial stimulation [135,136]. CRH enhances inflammation in LPS-treated immortal JAWS II cells, a known DC cell line derived from BMDCs of a C57BL/6 p53-knockout mouse, and murine mesenteric lymph node-derived dendritic cells, via distinct CRHR1-dependent mechanisms, that include stimulation of T-cell proliferation, elevation of IL-6 and MIP-1α secretion and reduction in the anti-inflammatory IL-4 levels [17,113,134]. In addition, treatment of human monocyte-derived dendritic cells with CRH attenuated IL-18 production which has an anti-inflammatory action [137].…”

Involvement of Corticotropin-Releasing Factor and Receptors in Immune Cells in Irritable Bowel Syndrome

“…Commensal bacterial strains can stimulate the production of CRF in dendritic cell, showing that CRF derived from dendritic cell may be involved in the pathogenesis of IBS ( 36 , 37 ). JAWSII cells and mouse mesenteric lymph node-dendritic cells expressed CRFR1 and CRFR2 receptors ( 30 , 38 ). CRF promotes inflammation in mature JAWSII by increasing the production of proinflammatory IL-6 and MIP-1α and decreasing anti-inflammatory IL-4 ( 30 ).…”

“…CRF promotes inflammation in mature JAWSII by increasing the production of proinflammatory IL-6 and MIP-1α and decreasing anti-inflammatory IL-4 ( 30 ). CRF increases the capacity of mouse mesenteric lymph node-dendritic cells to stimulate T-cell proliferation, and treatment of mesenteric lymph node-dendritic cells with CRFR1 antagonist yielded a reduced capacity to stimulate T cells ( 38 ).…”