Abstract
Sex hormone has become a “hot topic” to evaluate the hormonal therapeutic potential in severe asthma. Th17 cell is one of the main influencing factors involved in the pathogenesis of severe asthma, hence also called as kernel of severe asthma, and Th17 subtype of non-T2 asthma is less responsive (resistance) to inhaled corticosteroid (ICS), so severe in nature. Methyl-CpG binding domain protein 2 (MBD2) is overexpressed and regulates the Th17 differentiation, showing the possibility of therapeutic target in treating Th17 mediated severe asthma. Sex hormone fluctuates at the different physiobiological conditions of the human body and affects the asthma pathobiology showing its role in asthma prevalence, severity, remission, and therapy. This review briefly overviews the sex hormones, their influence in asthma at the different physiobiological conditions of human body, and MBD2 severe asthma connection with the possible therapeutic potential of sex steroids in MBD2 mediated Th17 predominant severe asthma. Male sex hormone tends to show a beneficial effect and possibly downregulates the expression of Th17 cells via regulating MBD2 through a mechanism distinct from corticosteroid treatment and guides us towards discovery of new therapeutic agent, reduces the asthma-related complications, and promotes long-term survival by lowering the risk of therapy-resistant issues of old age severe asthma.
Highlights
Asthma is a complex, chronic, heterogenous inflammatory disease, with diverse endotypes and phenotypes, characterized by airway inflammation and airway hyper-responsiveness (AHR), relieved spontaneously or by medications [1]
T2 asthma, childhood predominant, is better recognized, and several targeted monoclonal antibodies are identified for therapy
Non-T2 asthma, usually adult-onset/old age predominant, is still obscure with neutrophilic, paucigranulocytic, or mixed subtypes, where inflammation is driven through varieties of asthma-related inflammatory cells, and with airway muscular, neural, or comorbidities association [3, 4]
Summary
Chronic, heterogenous inflammatory disease, with diverse endotypes and phenotypes, characterized by airway inflammation and airway hyper-responsiveness (AHR), relieved spontaneously or by medications [1]. Proinflammatory cytokines, oxidative stress, neuronal and hormonal responses, and epigenetic regulation are involved in Th17 cell-mediated severe asthma, but the underlying mechanisms are still unknown. Medications Hormone Replacement erapy (HRT) Oral Contraceptive Pills (OCP) Aspirin It is a well-known fact that the loss of MBD2 inclines towards Th2 cellular polarization [7] and deficiency in Th17 differentiation. Our initial study in patients showed increased expression of MBD2 in Th17 mediated severe asthma from peripheral blood samples. We found the increased MBD2 expression after stimulus differentiation in splenic CD4+ T-cells in our animal model, showing involvement of MBD2 in immunological pathogenesis of Th17 mediated neutrophilic severe asthma and differentiation of CD4+ T-cells. IL-17A production with IL-17A mediated airway inflammation and IL23R expression is increased by estrogen and progesterone [12]. This review briefly overviews the sex hormones, their influence in asthma at different physiobiological conditions of the human body, MBD2 severe asthma association from various studies, and role of sex hormones in the MBD2 expression with the possible therapeutic potential of sex steroids in MBD2 mediated Th17 predominant severe asthma
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