DM‐induced Hypermethylation of IR and IGF1R attenuates mast cell activation and airway responsiveness in rats

Individuals with Mast Cell Activation Syndrome (MCAS), a rare chronic disease, experience unpredictable physical symptoms and diagnostic challenges resulting in poor emotional states. The prevalence and correlates of depressive symptoms were examined among 125 participants who completed the CES-D and relevant instruments. The majority reported a clinically-significant level of depression which was especially common among younger participants and those who reported greater loneliness or more disease-specific stressors. Greater magnitude of depressive symptoms was associated with greater illness intrusiveness, less social support, and lower optimism. Results highlight the value of interventions targeting loneliness and stressors unique to this population.

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Brain mast cells link the immune system to anxiety-like behavior

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0809479105 ◽

2008 ◽

Vol 105 (46) ◽

pp. 18053-18057 ◽

Cited By ~ 108

Author(s):

Katherine M. Nautiyal ◽

Ana C. Ribeiro ◽

Donald W. Pfaff ◽

Rae Silver

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Cell Activation ◽

Mast Cell Activation ◽

Neural Systems ◽

Loss Of Function ◽

Littermate Control ◽

Cytokines And Chemokines ◽

Function Models ◽

The Brain

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient KitW−sh/W−sh (sash−/−) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links.

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Association of Mast Cell Burden and TIM-3 Expression with Recalcitrant Chronic Rhinosinusitis with Nasal Polyps

Annals of Otology Rhinology & Laryngology ◽

10.1177/0003489421995038 ◽

2021 ◽

pp. 000348942199503

Author(s):

Michael A. Belsky ◽

Erica Corredera ◽

Hridesh Banerjee ◽

John Moore ◽

Li Wang ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Cell Activation ◽

Enzymatic Digestion ◽

Sinus Surgery ◽

Mast Cell Activation ◽

Need For Treatment ◽

Inflammatory State

Objectives: Previous work showed that higher polyp mast cell load correlated with worse postoperative endoscopic appearance in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyp epithelial mast cells showed increased expression of T-cell/transmembrane immunoglobulin and mucin domain protein 3 (TIM-3), a receptor that promotes mast cell activation and cytokine production. In this study, CRSwNP patients were followed post-operatively to investigate whether mast cell burden or TIM-3 expression among mast cells can predict recalcitrant disease. Methods: Nasal polyp specimens were obtained via functional endoscopic sinus surgery (FESS) and separated into epithelial and stromal layers via enzymatic digestion. Mast cells and TIM-3-expressing mast cells were identified via flow cytometry. Mann-Whitney U tests and Cox proportional hazard models assessed whether mast cell burden and TIM-3 expression were associated with clinical outcomes, including earlier recurrence of polypoid edema and need for treatment with steroids. Results: Twenty-three patients with CRSwNP were studied and followed for 6 months after undergoing FESS. Higher mast cell levels were associated with earlier recurrence of polypoid edema: epithelial HR = 1.283 ( P = .02), stromal HR = 1.103 ( P = .02). Percent of mast cells expressing TIM-3 in epithelial or stromal layers was not significantly associated with earlier recurrence of polypoid edema. Mast cell burden and TIM-3+ expression were not significantly associated with need for future treatment with steroids post-FESS. Conclusions: Mast cell load in polyp epithelium and stroma may predict a more refractory postoperative course for CRSwNP patients. The role of TIM-3 in the chronic inflammatory state seen in CRSwNP remains unclear.

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