Mast cell-derived serine proteinase regulates T helper 2 polarization

Liu, Zhiqiang; Song, Jiangping; Liu, Xiaoyu; Jiang, Jing; Chen, Xiao; Yang, Litao; Hu, Tian‐Yong; Zheng, Peng‐Yuan; Liu, Zhigang; Yang, Ping‐Chang

doi:10.1038/srep04649

Cited by 24 publications

(22 citation statements)

References 27 publications

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“…It is worth noting that MCs have been described as modulating the T cell response patterns, sometimes favoring a Th2 profile ( 42 , 43 ), but also of Th1 ( 44 ) and Th17 ( 45 ). However, this modulatory activity has been consistently associated with MC degranulation, which we did not detect, whereas the effects we describe were induced by direct cell contact between MCs and DCs.…”

Section: Discussionmentioning

confidence: 99%

Tolerogenic IDO+ Dendritic Cells Are Induced by PD-1-Expressing Mast Cells

et al. 2016

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Mast cells (MCs) are tissue resident cells, rich in inflammatory mediators, involved in allergic reactions, and with an increasingly recognized role in immunomodulation. Dendritic cells (DCs), on the other hand, are central to the determination of immune response patterns, being highly efficient antigen-presenting cells that respond promptly to changes in their microenvironment. Here, we show that direct cell contact between immature monocyte-derived DCs (iDCs) and MC bends DCs toward tolerance induction. DCs that had direct contact with MC (MC-iDC) decreased HLA-DR but increased PD-L1 expression and stimulated regulatory T lymphocytes, which expresses FoxP3+, secrete TGF-β and IL-10, and suppress the proliferation of mitogen-stimulated naïve T lymphocytes. Furthermore, MC-iDC expressed higher levels of indoleamine-2,3-deoxigenase (IDO), a phenomenon that was blocked by treatment of MC with anti-PD-1 or by the treatment of DCs with anti-PD-L1 or anti-PD-L2, but not by blocking of H1 and H2 histamine receptors on DCs. Contact with MC also increased phosphorylated STAT-3 levels in iDCs. When a STAT-3 inhibitor, JSI-124, was added to the DCs before contact with MC, the MC-iDC recovered their ability to induce allogeneic T cell proliferation and did not increase their IDO expression.

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Section: Discussionmentioning

confidence: 99%

Tolerogenic IDO+ Dendritic Cells Are Induced by PD-1-Expressing Mast Cells

et al. 2016

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“…Yet, the remedies used to modulate the aberrant cytokine expression in IBD are limited at the time being. Published data indicate that the Th2 cells in subjects with immune disorders can be converted to Tregs [ 16 ]. Vitamin D can promote the generation of Treg [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

A vitamin D receptor agonist converts CD4+ T cells to Foxp3+ regulatory T cells in patients with ulcerative colitis

Lan

Din

et al. 2017

Oncotarget

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One of the pathological features of ulcerative colitis (UC) is the dysfunction of immune regulatory T cells (Treg cells); the pathogenesis is unclear and needs to be further investigated. Vitamin D has immune regulatory functions. This study tests a hypothesis that vitamin D receptor (VDR) regulates Treg cell differentiation. Peripheral blood samples were collected from UC patients and healthy subjects. The correlation between VDR expression and T helper (Th)2 cell differentiation in peripheral CD4+ T cells was analyzed. We observed that the expression of VDR was lower, the expression of interleukin (IL)-4 was higher, in peripheral CD4+ T cells of UC patients than that in healthy controls. Naive CD4+ T cells from VDR deficient mice were prone to differentiating into Th2 cells, which could be adjusted by the presence of VDR agonists. The Th2 polarization status in the peripheral CD4+ T cells of UC patients could be converted to regulatory T cells in the culture in the presence of VDR agonists. In conclusion, the peripheral Th2 cells in UC patients can be converted to regulatory T cells by VDR agonists in the culture. The results suggest that administration of VDR agonists at proper dosages may improve the immunity of UC patients.

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“…The latter suppressed the expression of Th2 cytokines and increased the expression of Foxp3 genes in Th2 cells, which contributed to the immune regulatory properties similar to regulatory T cells. 73 Although MCs play an immunomodulatory role in the gut, how this mechanism action works in IBS is unknown, and needs more interpretation.…”

Section: Mast Cells In Gut Immunomodulation and Inflammationmentioning

confidence: 99%

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Zhang

Song

Hou

2016

J Neurogastroenterol Motil

111

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Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder since it lacks demonstrable pathological abnormalities. However, in recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel, has been observed in some patients with IBS. The close association of mast cells with major intestinal functions, such as epithelial secretion and permeability, neuroimmune interactions, visceral sensation, and peristalsis, makes researchers and gastroenterologists to focus attention on the key roles of mast cells in the pathogenesis of IBS. Numerous studies have been carried out to identify the mechanisms in the development, infiltration, activation, and degranulation of intestinal mast cells, as well as the actions of mast cells in the processes of mucosal barrier disruption, mucosal immune dysregulation, visceral hypersensitivity, dysmotility, and local and central stress in IBS. Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients, and have partially exhibited considerable efficacy. This review focuses on recent advances in the role of mast cells in IBS, with particular emphasis on bridging experimental data with clinical therapeutics for IBS patients.

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Mast cell-derived serine proteinase regulates T helper 2 polarization

Cited by 24 publications

References 27 publications

Tolerogenic IDO+ Dendritic Cells Are Induced by PD-1-Expressing Mast Cells

Tolerogenic IDO+ Dendritic Cells Are Induced by PD-1-Expressing Mast Cells

A vitamin D receptor agonist converts CD4+ T cells to Foxp3+ regulatory T cells in patients with ulcerative colitis

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

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