Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns

Galli, Stephen J.; Gaudenzio, Nicolas; Tsai, Mindy

doi:10.1146/annurev-immunol-071719-094903

Cited by 195 publications

(167 citation statements)

References 180 publications

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“…In this study, in vitro-cultured BMMCs were shown to produce the cytokines IL-6 and TNF-α in response to rVSVΔM51. We could not detect significant cytokine expression by BMMCs earlier than 12 h after infection with rVSVΔM51, suggesting that the cytokines were generated as a consequence of de novo synthesis rather than being released from pre-formed pools [53]. A modest but statistically significant release of IL-6 and TNF-α in response to rVSVΔM51 was observed at 12 h post-infection, which peaked by 16 h and declined by 20 h post-infection.…”

Section: Discussionmentioning

confidence: 66%

Type I Interferon α/β Receptor-Mediated Signaling Negatively Regulates Antiviral Cytokine Responses in Murine Bone-Marrow-Derived Mast Cells and Protects the Cells from Virus-Induced Cell Death

Darzianiazizi

Mehrani

Chan

et al. 2020

IJMS

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Mast cells (MCs) are critical for initiating inflammatory responses to pathogens including viruses. Type I interferons (IFNs) that exert their antiviral functions by interacting with the type I IFN receptor (IFNAR) play a central role in host cellular responses to viruses. Given that virus-induced excessive toxic inflammatory responses are associated with aberrant IFNAR signaling and considering MCs are an early source of inflammatory cytokines during viral infections, we sought to determine whether IFNAR signaling plays a role in antiviral cytokine responses of MCs. IFNAR-intact, IFNAR-blocked, and IFNAR-knockout (IFNAR-/-) bone-marrow-derived MCs (BMMCs) were treated in vitro with a recombinant vesicular stomatitis virus (rVSVΔm51) to assess cytokine production by these cells. All groups of MCs produced the cytokines interleukin-6 and tumor necrosis factor-α in response to rVSVΔm51. However, production of the cytokines was lowest in IFNAR-intact cells as compared with IFNAR-/- or IFNAR-blocked cells at 20 h post-stimulation. Surprisingly, rVSVΔm51 was capable of infecting BMMCs, but functional IFNAR signaling was able to protect these cells from virus-induced death. This study showed that BMMCs produced pro-inflammatory cytokines in response to rVSVΔm51 and that IFNAR signaling was required to down-modulate these responses and protect the cells from dying from viral infection.

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Section: Discussionmentioning

confidence: 66%

Type I Interferon α/β Receptor-Mediated Signaling Negatively Regulates Antiviral Cytokine Responses in Murine Bone-Marrow-Derived Mast Cells and Protects the Cells from Virus-Induced Cell Death

Darzianiazizi

Mehrani

Chan

et al. 2020

IJMS

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“…Mast cells are markers for allergic and inflammatory responses. 35 The absence of inflammatory mRNA markers or mast cell numbers in the lungs after miR96 indicates that miR96 itself does not cause any off-target inflammation that may be detrimental to the health of the animal. This suggests that direct delivery of the miR96 mimic to the lungs may prevent excessive off-target effects that may be produced by intravenous delivery or other approaches.…”

Section: Discussionmentioning

confidence: 99%

Direct Delivery of MicroRNA96 to the Lungs Reduces Progression of Sugen/Hypoxia-Induced Pulmonary Hypertension in the Rat

Docherty

Denver

Fisher

et al. 2020

Molecular Therapy - Nucleic Acids

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The 5HT1B receptor (5HT1BR) contributes to the pathogenic effects of serotonin in pulmonary arterial hypertension. Here, we determine the effect of a microRNA96 (miR96) mimic delivered directly to the lungs on development of severe pulmonary hypertension in rats. Female rats were dosed with sugen (30 mg/kg) and subjected to 3 weeks of hypobaric hypoxia. In normoxia, rats were dosed with either a 5HT1BR antagonist SB216641 (7.5 mg/kg/day for 3 weeks), miR96, or scramble sequence (50 μg per rat), delivered by intratracheal (i.t) administration, once a week for 3 weeks. Cardiac hemodynamics were determined, pulmonary vascular remodeling was assessed, and gene expression was assessed by qRT-PCR, and in situ hybridization and protein expression were assessed by western blot and ELISA. miR96 expression was increased in pulmonary arteries and associated with a downregulation of the 5HT1BR protein in the lung. miR96 reduced progression of right ventricular systolic pressure, pulmonary arterial remodeling, right ventricular hypertrophy, and the occurrence of occlusive pulmonary lesions. Importantly, miR96 had no off-target effects and did not affect fibrotic markers of liver and kidney function. In conclusion, direct delivery of miR96 to the lungs was effective, reducing progression of sugen/hypoxia-induced pulmonary hypertension with no measured off-target effects. miR96 may be a novel therapy for pulmonary arterial hypertension, acting through downregulation of 5HT1BR.

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“…Given the broad distribution of MCs and their multifunctional role, they have been implicated in many diseases beyond allergy [20][21][22] . For example, recent reviews highlight the role of MCs in cardiovascular diseases 23 , cancer 24 , airway diseases 25 , as well as in viral, bacterial and fungal infections [26][27][28] .…”

Section: Introductionmentioning

confidence: 99%

The Ingenious Mast Cell: Contemporary insights into mast cell behavior and function

Dahlin¹,

Maurer²,

Metclafe³

et al. 2020

Preprint

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Mast cells are (in)famous for their role in allergic diseases, but the physiological and pathophysiological roles of this ingenious cell are still not fully understood. Mast cells are important for homeostasis and surveillance of the human system, recognizing both endogenous and exogenous agents, which induce release of a variety of mediators acting on both immune and non-immune cells, including nerve cells, fibroblasts, endothelial cells, smooth muscle cells and epithelial cells. During recent years, clinical and experimental studies on human mast cells as well as experiments using animal models have resulted in many discoveries that help decipher the function of mast cells in health and disease. In this review we focus particularly on new insights into mast cell biology, with a focus on mast cell development, recruitment, heterogeneity and reactivity. We also highlight the development in our understanding of mast cell driven-diseases and discuss the development of novel strategies to treat such conditions.

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Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns

Cited by 195 publications

References 180 publications

Type I Interferon α/β Receptor-Mediated Signaling Negatively Regulates Antiviral Cytokine Responses in Murine Bone-Marrow-Derived Mast Cells and Protects the Cells from Virus-Induced Cell Death

Type I Interferon α/β Receptor-Mediated Signaling Negatively Regulates Antiviral Cytokine Responses in Murine Bone-Marrow-Derived Mast Cells and Protects the Cells from Virus-Induced Cell Death

Direct Delivery of MicroRNA96 to the Lungs Reduces Progression of Sugen/Hypoxia-Induced Pulmonary Hypertension in the Rat

The Ingenious Mast Cell: Contemporary insights into mast cell behavior and function

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