Research of Amarjit Mishra on Immunometabolism driving allergic asthma
Breathing is what makes all living beings stay alive. A determinant characteristic of living beings, breathing is one of the primary functions performed by the body and any disorder related to it is bound to have a long-term impact on the health.
Asthma is one such disorder that is much more common than it is thought of. Simply translated as ‘difficulty in breathing’, in fact asthma is a much more complex disorder. Caused by various factors, asthma is often responsible for causing breathing troubles in living beings, especially humans. One of the least studied phenomena is the link between asthma and allergies.
Allergies often considered to be a phenomenon distinct from asthma, scientists have proven that there is a point where the two concepts emerge and give rise to a disease known as the allergy-induced asthma. One of the scientists who has done extensive research work in enhancing the understanding of this disease is the famous Veterinarian research scientist-turned-pulmonologist Amarjit Mishra.
Amarjit Mishra is currently working as an Assistant Professor at Auburn University in Alabama in the United States of America. This article tends to explore the link between asthma and allergy, according to the results obtained by the research conducted by Amarjit Mishra and his team.
Auburn University Professor Amarjit Mishra Explains about Asthma and Allergy Symptoms
On the surface, one of the similarities between allergies and asthma is that both conditions set off the body's defense mechanisms. But there appears to be a more complex connection between the two. Although allergies can affect every sense organ, there is a specific type of allergy that affects the respiratory system and makes breathing difficult.
Asthma and allergy symptoms coexist in this way. This type of respiratory condition, also known as allergy-induced asthma or allergic asthma, is brought on by typical allergens including dust mites, pollen, and pet dander. These allergens produce allergic rhinitis symptoms in humans when they enter the respiratory system. When these allergens enter the respiratory system of a human it triggers symptoms similar to that of allergic rhinitis. Being foreign particles, the allergens act as a trigger to activate the immune system leading to the release of antibodies.
These antibodies then further bind to the allergens, sparking a chain of subsequent events. Even skin or food allergies have been discovered to trigger asthma-like symptoms in certain individuals. Your immune system's production of chemicals causes allergy symptoms and signs like runny nose, itchy eyes, and skin rashes. Some others experience the similar reaction in their lungs and airways, which causes symptoms of asthma.
Several immunological mechanisms are involved in this allergy-induced asthma. The pathway has been better understood thanks in large part to Amarjit Mishra, who has also suggested potential therapeutic alternatives for those suffering from the pathological condition known as allergy-induced asthma.
The immune response to disorders such as allergy-induced asthma is majorly due to various biochemicals For instance, IgE or Immunoglobulin E is a highly potent biochemical that is released by the body when any danger is encountered or perceived from foreign matter. IgE not only protects the body but creates an additional layer of defense for subsequent infections causing disease.
Similarly, many biochemicals are involved in the pathogenesis of allergy-induced asthma. This kind of asthma is in fact the most popular form of asthma. More than sixty percent of asthmatic people across the world are known to have allergens as a major trigger point for their asthma. The symptoms associated with this kind of asthma are often more severe. During an asthma attack caused by allergens, the air passage gets contracted and there is an increased pressure on the chest which makes it difficult for the patient to breathe. This may be accompanied by wheezing and coughing.
The Cellular Links
The majority of asthmatic adults and children suffer from allergic asthma, which is the most common type of asthma. Researchers like Amarjit Mishra, Yunqin Shen, Zongpei Lian, and many others have been working to understand the pathophysiological causes of these variations among asthmatic patients. An important stage in the start of allergic asthma has been identified as the formation of allergen-specific CD4+ T helper type 2 (Th2) cells.
In murine models and in people with allergic asthma, Th2 cells are the main source of the type 2 cytokines IL4, IL5, and IL13 that coordinate allergic inflammation of the airways. Based on control, patients with mild asthma may move into the severe category. Despite having a modest condition at baseline, some of the individuals are vulnerable to adverse outcomes, including deadly asthma episodes. Furthermore, it's thought that lung infections in people with asthma have a complex immune response and are linked to Th1/Th17 immunity rather than traditional Th2 immunity, which causes neutrophils rather than eosinophils to infiltrate the airways.
Discovery by Amarjit Mishra and His Team
Amarjit Mishra and his team have discovered via their research that Th2-high asthma is characterised by raised levels of serum IgE, eosinophils in the blood and sputum, fractional exhaled nitric oxide, and type 2 cytokines IL4, IL5, and IL13.
Natural killer cells and innate type 2 lymphoid cells control the innate Type 2 inflammatory response in the airways, whereas Th2 (T helper type 2) immune cells in the lungs develop adaptive immunity. Nevertheless, IL-5, IL-13, and IL-4 cytokine production are accompanied with an eosinophilic inflammatory phenotype as a result of the Th2-mediated lung adaptive immune response.
Moreover, Amarjit Mishra of Auburn University discovered that antigen-presenting DC that depends on immature mitochondrial oxidative phosphorylation (OXPHOS) and is controlled by AMPK signalling initiates allergen-induced Th2 inflammation. Early Toll-like receptor (TLR) activation causes DC to undergo metabolic reprogramming along with an increase in glycolysis for the synthesis of ATP.
In the presence of 2-deoxyglucose (2-DG), a glucose analogue, the immunological priming function, CCR7-dependent movement, and antigen-presentation capacity of DC were noticeably diminished. Additionally, CCR7 expression and oligomerization are hindered in DC lacking hypoxia-inducible factor (HIF1), showing that effector functions are regulated by the metabolic flexibility of DC. Recent research by Amarjit Mishra, an assistant professor, and his colleagues has demonstrated that acute asthma induces pyruvate kinase M2 (PKM2) in CD11c+ APCs, an enzyme that is necessary for the conversion of phosphoenolpyruvate to pyruvate during glycolysis.
Furthermore, through inhibiting STAT3 phosphorylation and IL-1-mediated TSLP release, activation of PKM2 by the small molecule activator TEPP46 significantly reduced house dust mite (HDM)-induced eosinophilic airway inflammation, subepithelial collagen deposition, and mucous metaplasia. It's interesting to note that TSLP release and subsequent airway inflammation are controlled by the redox regulation of the glycolytic enzyme PKM2 via glutathionylation, demonstrating that metabolic modifications are a precursor to Th2 inflammation in asthma.
The aforementioned findings by Amarjit Mishra have a significant impact on how asthma and allergies are related, as well as how Th2 inflammation plays a role in the aetiology and functional presentation of allergic-induced asthma. Such discoveries have a great deal of promise for the search for disease-treating medicinal options.
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