Production of corticotropin-releasing factor and urocortin from human monocyte-derived dendritic cells is stimulated by commensal bacteria in intestine

Koido, Shigeo; Ohkusa, Toshifumi; Kan, Shin; Takakura, Kazuki; Saito, Keisuke; Komita, Hideo; Ito, Zensho; Kobayashi, Hiroko; Takami, Shiro; Uchiyama, Kan; Arakawa, Hiroshi; Ito, Masaki; Okamoto, Masato; Kajihara, Mikio; Homma, Sadamu; Tajiri, Hisao

doi:10.3748/wjg.v20.i39.14420

Cited by 21 publications

(11 citation statements)

References 36 publications

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“…Various stimulants or stressors including phytohemagglutinin, concanavalin A, and IL-2, induce lymphocytes to express CRH mRNA and/or CRH protein 153 . Human monocyte- derived dendritic cells produce CRH mRNA and protein when stimulated by the intestinal commensal bacteria bacteroides vulgatus and fusobacterium varium 154 . Production of PGE2 by explants of RA synovial tissue is increased in the presence of CRH 155 .…”

Section: Expression Of Crh and Pomc In The Immune System And The Skinmentioning

confidence: 99%

Extra-adrenal glucocorticoid biosynthesis: implications for autoimmune and inflammatory disorders

et al. 2020

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Glucocorticoid synthesis is a complex, multistep process that starts with cholesterol being delivered to the inner membrane of mitochondria by StAR and StAR-related proteins. Here its side chain is cleaved by CYP11A1 producing pregnenolone. Pregnenolone is converted to cortisol by the enzymes 3-βHSD, CYP17A1, CYP21A2 and CYP11B1. Glucocorticoids play a critical role in the regulation of the immune system and exert their action through the glucocorticoid receptor (GR). Although corticosteroids are primarily produced in the adrenal gland, they can also be produced in a number of extra-adrenal tissue including the immune system, skin, brain, and intestine. Glucocorticoid production is regulated by ACTH, CRH, and cytokines such as IL-1, IL-6 and TNFα. The bioavailability of cortisol is also dependent on its interconversion to cortisone which is inactive, by 11βHSD1/2. Local and systemic glucocorticoid biosynthesis can be stimulated by ultraviolet B, explaining its immunosuppressive activity. In this review, we want to emphasize that dysregulation of extra-adrenal glucocorticoid production can play a key role in a variety of autoimmune diseases including multiple sclerosis (MS), lupus erythematosus (LE), rheumatoid arthritis (RA), and skin inflammatory disorders such as psoriasis and atopic dermatitis (AD). Further research on local glucocorticoid production and its bioavailability may open doors into new therapies for autoimmune diseases.

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Section: Expression Of Crh and Pomc In The Immune System And The Skinmentioning

confidence: 99%

Extra-adrenal glucocorticoid biosynthesis: implications for autoimmune and inflammatory disorders

et al. 2020

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“…In addition, DCs may secrete corticotropin-releasing factor that can induce alterations in intestinal motility and visceral hypersensitivity. Two studies with mouse DCs and human peripheral blood monocyte-derived DCs presented increased levels of corticotropin-releasing factor after stimulation by some commensal bacterial strains [ 101 , 102 ]. In a Scandinavian study, 10 patients with self-reported food hypersensitivity were recruited and 9 of them tested positive for IBS according to the Rome II criteria.…”

Section: Innate Immune Activationmentioning

confidence: 99%

Current insights into the innate immune system dysfunction in irritable bowel syndrome

Lazaridis

2018

aog

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Irritable bowel syndrome (IBS) is a functional bowel disorder associated with abdominal pain and alterations in bowel habits. The presence of IBS greatly impairs patients’ quality of life and imposes a high economic burden on the community; thus, there is intense pressure to reveal its elusive pathogenesis. Many etiological mechanisms have been implicated, but the pathophysiology of the syndrome remains unclear. As a result, novel drug development has been slow and no pharmacological intervention is universally accepted. A growing evidence implicates the role of low-grade inflammation and innate immune system dysfunction, although contradictory results have frequently been presented. Mast cells (MC), eosinophils and other key immune cells together with their mediators seem to play an important role, at least in subgroups of IBS patients. Cytokine imbalance in the systematic circulation and in the intestinal mucosa may also characterize IBS presentation. Toll-like receptors and their emerging role in pathogen recognition have also been highlighted recently, as dysregulation has been reported to occur in patients with IBS. This review summarizes the current knowledge regarding the involvement of any immunological alteration in the development of IBS. There is substantial evidence to support innate immune system dysfunction in several IBS phenotypes, but additional studies are required to better clarify the underlying pathogenetic pathways. IBS heterogeneity could potentially be attributed to multiple causes that lead to different disease phenotypes, thus explaining the variability found between study results.

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“…Besides, recently, there have been reports of autocrine effects of CRF on dendritic cells. 31,32 It had been proved that commensal bacteria such as…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Wang

et al. 2015

J Neurogastroenterol Motil

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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

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Production of corticotropin-releasing factor and urocortin from human monocyte-derived dendritic cells is stimulated by commensal bacteria in intestine

Cited by 21 publications

References 36 publications

Extra-adrenal glucocorticoid biosynthesis: implications for autoimmune and inflammatory disorders

Extra-adrenal glucocorticoid biosynthesis: implications for autoimmune and inflammatory disorders

Current insights into the innate immune system dysfunction in irritable bowel syndrome

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

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