Corticotropin-releasing Factor Changes the Phenotype and Function of Dendritic Cells in Mouse Mesenteric Lymph Nodes.
- Author:
Li MENG
1
;
Zhang LU
;
Wang XIAOTENG
;
Hu YUE
;
Lu BIN
;
Meng LINA
;
Chen ZHE
Author Information
- Publication Type:Original Article
- Keywords: Corticotropin-releasing hormone; Dendritic cells; Immunity, cellular
- MeSH: Animals; Blotting, Western; Cell Proliferation; Corticotropin-Releasing Hormone*; Dendritic Cells*; Fluorescent Antibody Technique; Immunity, Cellular; Lymph Nodes*; Lymphocyte Culture Test, Mixed; Mice*; Pathology; Phenotype*; Polymerase Chain Reaction; Receptors, Corticotropin-Releasing Hormone; T-Lymphocytes
- From:Journal of Neurogastroenterology and Motility 2015;21(4):571-580
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/AIMS: Dendritic 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. METHODS: Mouse 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. RESULTS: Immunofluorescent 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: CRF can alter the phenotype and function of intestinal DCs through direct action on CRF-R1 and CRF-R2, and activation of the CRF-R1 and CRF-R2 pathways yields opposing outcomes.
