PMID- 26424042 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20151001 LR - 20200930 IS - 2093-0879 (Print) IS - 2093-0887 (Electronic) IS - 2093-0879 (Linking) VI - 21 IP - 4 DP - 2015 Oct 1 TI - Corticotropin-releasing Factor Changes the Phenotype and Function of Dendritic Cells in Mouse Mesenteric Lymph Nodes. PG - 571-80 LID - 10.5056/jnm15019 [doi] AB - 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. FAU - Meng, Li AU - Meng L AUID- ORCID: 0000-0001-8921-2533 AD - Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. FAU - Lu, Zhang AU - Lu Z AD - Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. FAU - Xiaoteng, Wang AU - Xiaoteng W AD - Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. FAU - Yue, Hu AU - Yue H AD - Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. FAU - Bin, Lu AU - Bin L AUID- ORCID: 0000-0002-3381-6976 AD - Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. FAU - Lina, Meng AU - Lina M AD - Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. FAU - Zhe, Chen AU - Zhe C AD - Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. LA - eng PT - Journal Article PL - Korea (South) TA - J Neurogastroenterol Motil JT - Journal of neurogastroenterology and motility JID - 101530189 PMC - PMC4622140 OTO - NOTNLM OT - Corticotropin-releasing hormone OT - Dendritic cells OT - Immunity OT - cellular EDAT- 2015/10/02 06:00 MHDA- 2015/10/02 06:01 PMCR- 2015/10/01 CRDT- 2015/10/02 06:00 PHST- 2015/01/30 00:00 [received] PHST- 2015/06/11 00:00 [revised] PHST- 2015/06/30 00:00 [accepted] PHST- 2015/10/02 06:00 [entrez] PHST- 2015/10/02 06:00 [pubmed] PHST- 2015/10/02 06:01 [medline] PHST- 2015/10/01 00:00 [pmc-release] AID - jnm15019 [pii] AID - jnm-21-571 [pii] AID - 10.5056/jnm15019 [doi] PST - ppublish SO - J Neurogastroenterol Motil. 2015 Oct 1;21(4):571-80. doi: 10.5056/jnm15019.