Preliminary study of histamine H 4 receptor expressed on human CD4 + T cells and its immunomodulatory potency in the IL-17 pathway of psoriasis

Han, Song; Hur, Min; Kim, Min Jung; Kim, Bo Mi; Kim, Kyoung Woon; Kim, Hae Rim; Choe, Yong Beom; Ahn, Kyu Joong; Lee, Yang Won

doi:10.1016/j.jdermsci.2017.05.011

Cited by 11 publications

(5 citation statements)

References 29 publications

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“…14 Similarly, H 4 receptor expression has also been reported in peripheral CD4 + T cells isolated from the blood of patients with psoriasis as well as in dermal CD4 + T cells of psoriatic skin. 25 Using the PrimeFlow technology we could demonstrate that H 4 receptor mRNA is not homogeneously expressed in CD4 + T cells and confirmed findings obtained with other techniques that a higher proportion of CD4 + T cells derived from AD patients expresses H 4 receptor mRNA. Titration experiments with in vitro differentiated TH2 cells further confirmed the finding that H 4 receptor expression is regulated through IL-4 stimulation.…”

Section: The Stimulation Of H 4 Receptor Results In Increased Il-5 An...supporting

confidence: 86%

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The stimulation of TH2 cells results in increased IL‐5 and IL‐13 production via the H₄ receptor

Nikolouli,

Mommert,

Dawodu

et al. 2024

Allergy

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BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease resulting in decreased quality of life. Histamine and specifically the H4 receptor play a key role in the inflammatory process in AD and serve as targets for novel therapeutic approaches.ObjectiveIn the present study we aimed to elucidate the immunopathological mechanisms with which the H4 receptor impacts TH2 cells and contributes to AD pathophysiology.MethodsTotal CD4+ T cells obtained from healthy or AD individuals and in vitro differentiated TH2 cells were cultured under different conditions and the mRNA expression or protein production of target molecules were determined using quantitative real‐time PCR and ELISA.ResultsH4 receptor mRNA expression was upregulated concentration dependent upon IL‐4 stimulation in in vitro differentiated TH2 cells progressively during the differentiation. Transcriptomic analysis of in vitro differentiated TH2 versus TH1 cells revealed that the H4 receptor among other genes represents one of the highly upregulated genes in TH2 cells.Most importantly, increased amounts of IL‐5 and IL‐13 mRNA expression were detected in in vitro differentiated TH2 cells as well as protein secretion in the presence of histamine or of the H4 receptor‐selective‐agonist when compared to the untreated control.ConclusionWe show for the first time an H4 receptor dependent upregulation of the pro‐inflammatory cytokines IL‐5 and IL‐13 in human TH2 cells by histamine. This suggests that the blockade of the H4 receptor may lead to downregulation of these cytokines and amelioration of AD symptoms as reported in first clinical studies.

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Section: The Stimulation Of H 4 Receptor Results In Increased Il-5 An...supporting

confidence: 86%

“…Previously we showed that CD4 + T cells from AD individuals express higher H 4 receptor mRNA levels 14 . Similarly, H 4 receptor expression has also been reported in peripheral CD4 + T cells isolated from the blood of patients with psoriasis as well as in dermal CD4 + T cells of psoriatic skin 25 …”

Section: Discussionsupporting

confidence: 59%

The stimulation of TH2 cells results in increased IL‐5 and IL‐13 production via the H₄ receptor

Nikolouli,

Mommert,

Dawodu

et al. 2024

Allergy

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“…H4R exerts immunoregulatory activities on leukocytes and represents an interesting target for immuno modulation. After the reference compound JNJ-7777120, further selective H4R antagonists 138 have been introduced into clinical development for distinct indications such as neurological disorders 139,140 , asthma 141,142 and for inflammatory skin disorders, including AD [143][144][145][146] . While H4R antagonism alone seems promising in reducing the scratching reaction in animal models of skin inflammation, it only improves inflammation in combination with H1R antagonism 147 .…”

Section: Restoring T Reg Cell Functionmentioning

confidence: 99%

Atopic dermatitis: an expanding therapeutic pipeline for a complex disease

Bieber

2021

Nat Rev Drug Discov

360

294

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“…CD4+ T cells differentiation into Th17 cells were performed according to previous report [19]. CD4+ T cells (5 × 10 5 ) were incubated for 48 h with anti-CD3 (1 μg/mL) (Abcam, USA), anti-CD28 antibody (1 μg/mL) (Abcam, USA), IL-1β (20 ng/mL)(Gibco, USA), IL-6 (20 ng/mL) (Gibco, USA), IL-23 (20 ng/mL) (Invitrogen, USA), IFN-γ-neutralizing antibody (2 μg/mL) (Cell Signaling Technology, USA), and IL-4-neutralizing antibody (2 μg/mL) (Cell Signaling Technology, USA).…”

Section: Methodsmentioning

confidence: 99%

LncRNA H19 over-expression inhibited Th17 cell differentiation to relieve endometriosis through miR-342-3p/IER3 pathway

Liu

Zhong

et al. 2019

Cell Biosci

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Objective To investigate the mechanism of LncRNA H19 in Th17 cell differentiation and endometrial stromal cells (ESCs) proliferation in endometriosis (EMS). Methods LncRNA H19, miR-342-3p and IER3 expressions were detected by qRT-PCR and western blot. The percentage of Th17 cells/CD4+ T cells was detected by flow cytometry. IL-17 level was measured by ELISA. The interaction of miR-342-3p and IER3 was confirmed by Luciferase reporter assay. Results LncRNA H19 and IER3 expressions were down-regulated in mononuclear cells from peritoneal fluid (PFMCs) of patients with EMS or under Th17 differentiation conditions, whereas miR-342-3p expression was up-regulated and the percentage of Th17 cells was increased in PFMCs of patients with EMS or under Th17 differentiation conditions. Over-expression of LncRNA H19 decreased IL-17 level and the percentage of Th17 cells/CD4+ T cells. Besides, we confirmed that miR-342-3p could target to IER3 and negatively regulate IER3 expression. LncRNA H19 over-expression suppressed Th17 differentiation and ESC proliferation through regulating miR-342-3p/IER3. In vivo experiments showed LncRNA H19 over-expression suppressed the growth of Th17 cell differentiation-induced endometriosis-like lesions. Conclusion LncRNA H19 was down-regulated in PFMC of patients with EMS or under Th17 polarizing conditions, and LncRNA H19 over-expression suppressed Th17 cell differentiation and ESCs proliferation through miR-342-3p/IER3 pathway.

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Preliminary study of histamine H 4 receptor expressed on human CD4 + T cells and its immunomodulatory potency in the IL-17 pathway of psoriasis

Cited by 11 publications

References 29 publications

The stimulation of TH2 cells results in increased IL‐5 and IL‐13 production via the H₄ receptor

The stimulation of TH2 cells results in increased IL‐5 and IL‐13 production via the H₄ receptor

Atopic dermatitis: an expanding therapeutic pipeline for a complex disease

LncRNA H19 over-expression inhibited Th17 cell differentiation to relieve endometriosis through miR-342-3p/IER3 pathway

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Preliminary study of histamine H 4 receptor expressed on human CD4 + T cells and its immunomodulatory potency in the IL-17 pathway of psoriasis

Cited by 11 publications

References 29 publications

The stimulation of TH2 cells results in increased IL‐5 and IL‐13 production via the H4 receptor

The stimulation of TH2 cells results in increased IL‐5 and IL‐13 production via the H4 receptor

Atopic dermatitis: an expanding therapeutic pipeline for a complex disease

LncRNA H19 over-expression inhibited Th17 cell differentiation to relieve endometriosis through miR-342-3p/IER3 pathway

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About

The stimulation of TH2 cells results in increased IL‐5 and IL‐13 production via the H₄ receptor

The stimulation of TH2 cells results in increased IL‐5 and IL‐13 production via the H₄ receptor