Ep. 7: “The Mechanisms of Itch” Featuring Drs. Isaac Chiu and Tiphaine Voisin
Jun 22, 2021
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Dr. Isaac Chiu, an expert on nervous system and inflammation, teams up with Dr. Tiphaine Voisin, a neuro-immunology specialist, to explore the fascinating world of itch. They delve into the complex relationship between sensory neurons and immune responses, revealing how leukotriene pathways trigger scratching behavior. The duo also discusses innovative therapeutic targets, including monoclonal antibodies, and the joy of blending science with personal creativity. Their insights shine a light on chronic itch and the potential for novel treatments.
T-cell behavior is significantly influenced by their priming location, highlighting the importance of spatial context in immunological responses.
COVID-19 induces a unique inflammatory response in the brain, marked by immune activation and distinct immune cell interactions not seen in other conditions.
Gut microbiome metabolites, such as acetate, play a crucial role in modulating intestinal innate immunity, revealing complex microbial-immune interactions.
Deep dives
Mechanisms of T-Cell Subtypes
Recent research highlights the influence of the site from which T-cells originate on their functional characteristics. The study notes that T-cells from different anatomical locations, such as inguinal and gut mesenteric lymph nodes, exhibit distinct profiles and behaviors influenced by their respective environments. For instance, RNA sequencing and surface marker analysis reveal that these T-cell populations behave uniquely based on their priming location rather than strictly adhering to the traditional TH1 or TH2 classifications. This suggests that the localization of T-cell activation fundamentally shapes their long-term functional properties, emphasizing the necessity to consider spatial context in immunological classifications.
COVID-19 and Neuroinflammation
The impact of COVID-19 on the brain is a significant area of investigation, revealing unique patterns of inflammation associated with infection. A detailed study examined brain samples from patients who died from COVID-19, comparing them to those from individuals with other respiratory issues. The findings indicated substantial immune activation and the presence of activated CD8 T-cells clustered with microglia, highlighting a distinctive inflammatory response not seen in other conditions like multiple sclerosis. This research deepens understanding of how COVID-19 can affect neural integrity and the overall pathology associated with the disease.
Microbiome-Derived Metabolism and Immunity
A fascinating study explores how metabolites produced by the gut microbiome, specifically acetate, influence intestinal innate immunity through a specific receptor. The research conducted in Drosophila shows that the acetate receptor TARG is crucial for activating immune responses in enterendocrine cells. This indicates that interactions between microbiome-derived metabolites and host immune signaling are more complex than previously understood, with innate immunity response being modulated by the microbiome's metabolic products. The implication is that understanding these pathways could lead to innovative approaches for regulating immunity based on microbial influences.
Neuroimmunology and Pain Perception
The interplay between the nervous system and immune responses is crucial in understanding sensations like pain and itch. This emerging field underscores the significance of crosstalk between sensory neurons and immune cells, particularly in mediating inflammatory responses. Recent discussions have highlighted how neurotransmitters and neuropeptides interact with immune mediators, regulating conditions such as chronic itch and pain. Research into these mechanisms reveals potential pathways for new treatments by targeting the signaling interactions between immune cells and neural pathways.
Therapeutic Implications for Chronic Itch
The identification of leukotriene pathways in chronic itch presents exciting new therapeutic avenues. Studies demonstrate that specific leukotrienes, particularly LTC4, actively induce scratching behavior in certain mouse models of dermatitis. The variations in immune cell activities during different phases of inflammation suggest that a tailored approach may be necessary for effective treatment of chronic itch. By understanding these pathways better, there is potential for developing new, targeted therapies that could alleviate the distress caused by chronic itch conditions.
Dr. Isaac Chiu is an Assistant Professor of Immunology at Harvard Medical School, studying the role of the nervous system in mediating inflammation and host defense. Dr. Tiphaine Voisin is a Postdoctoral Fellow at Harvard Medical School, specializing in somato-sensation and neuro-immunology. They recently published a paper in PNAS on the role of the CysLT2R receptor in acute and chronic itch.
COVID-19 Linked to Inflammation of the Brain – Scientists found that COVID-19 can spark a severe immune response in the central nervous system, affecting immune cells in the vascular system and brain.
