Role of Sex Hormones at Different Physiobiological Conditions and Therapeutic Potential in MBD2 Mediated Severe Asthma

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.

Androgen Plays a Potential Novel Hormonal Therapeutic Role in Th17 Cells Predominant Neutrophilic Severe Asthma by Attenuating BECs Regulated Th17 Cells Differentiation via MBD2 Expression

“…Subjects with severe asthma had increased neutrophils, lower FEV1, FEV1/FVC%, and FEV1%predicted ( Table 1 ). Interestingly, IgE and eosinophils levels were higher in the asthma group and much higher in the severe asthma group compared with the HC group because the severe asthma group also contains T2 severe asthma endotypes that predominantly have IgE and eosinophils as common biomarkers as shown from our previous study [ 16 ], and T2 and non-T2 asthma may also show mixed overlapping profiles in some cases [ 19 ].…”

“…The aggravation of asthma symptoms noted during the premenstrual and menstrual phase seems to be correlated with reduced testosterone level [ 27 ], showing that androgens might potentially be a therapeutic option. Recently, we reviewed the correlative association of Th17 cells, MBD2 expression, and sex hormones fluctuation status [ 19 ]. Therefore, we hypothesized that androgen has a potential therapeutic role in MBD2-mediated Th17 cells predominant neutrophilic severe asthma.…”

“…Does sex hormone down-regulate MBD2 expression or directly affects the differentiation and the expression of the Th17 cells in severe asthma as a therapeutic potential? In our recent review, we evaluated the correlative association of sex hormones fluctuation status, MBD2 expression, and Th17 cells, and postulated androgenic therapeutic potential in Th17 cells predominant neutrophilic severe asthma via regulating MBD2 [ 19 ], and here performed this study. First, we measured the androgen, the estrogen, and the androgen estrogen ratio in severe asthma subjects and correlated them with asthma status.…”

“…Sex hormones are not only involved in sex differentiation and reproduction, but are also involved in the regulation of immune response, and signaling pathways have become a "hot research topic" in asthma [17][18][19]. Estrogen and progesterone promote the differentiation of the Th17 cells, IL-17A-mediated airway inflammation, and IL23R expression through inhibiting let-7f microRNA expression [20,21].…”

Untargeted metabolomic analysis reveals different metabolites associated with response to mepolizumab and omalizumab in asthma

“…Androgens and androgen receptor expression have been postulated as underlying sex differences in asthma incidence [27][28][29]. Androgenic steroids inhibit the differentiation and reduce the number of ILC2 cells [30,31], which play a key role in asthma pathogenesis by releasing type 2 cytokines, IL-5 and IL-13, following activation by alarmins [32].…”