Title

One Mean Gene: How P2X3 Makes Asthma Worse in Women [online video]

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Original Publication Date

2021

Document Type

Presentation

Comments

7th Annual VCU 3MT® Competition, held on October 15, 2021.

Abstract

Kee's research involves mast cells, the primary immune cell involved with asthma and allergies. Her research shows that IL33 elicits an ATP release acting on the P2X3 receptor hypothesized only to be present females, creating a feed-forward loop, worsening inflammation in females than their male counterpart. This could explain why asthma is worse in females and also provides a therapeutic new target, P2X3, for developing drugs and blocking mast cell inflammation and finding a new cure for asthma and allergies.

Transcription

Ann Kee: If you're like me, you're one of the many Americans that suffer from asthma and allergies. In fact, it costs the U.S. over $80 billion a year due to missed work days, doctor's office visits, and medications. So it's really important we figure out how we can get this under control. Interestingly, women are 62% more likely than men to be diagnosed with asthma, and are three times more likely to be hospitalized for it. So what's the reason for this imbalance? That's where my research comes in. I study mast cells, the primary immune cell involved with asthma and allergies. Upon activation, mast cells release histamine and other inflammatory factors, ultimately leading to an allergic response. Which is why you take antihistamines. And which is why it's so important for us to study mast cell activation and how we can suppress it. It is known that IL 33, a mast cell activator, can elicit inflammation on its own. But, my research is the first to propose that IL 33 elicits an ATP release, acting on the P2X3 receptor, hypothesized only to be present in females, creating a feed forward loop worsening inflammation in females. So how can we study this? First, we can zoom in on the P2X3 receptor. We know it can be activated by ATP and, in return, elicit a calcium release. Calcium is so important for the cell because it contributes to many downstream signaling processes, ultimately leading to inflammation. Which is why you get that redness when you're having an allergic reaction. So, we take male and female mast cells from mice, give them ATP, and measure their calcium release. We see in my first graph that females, in pink, show robust release compared to males, in blue. This supports my hypothesis that P2X3 may only be present in females. Next, we can zoom out and look downstream at asthma- related cytokines. These are so important because they're one of the reasons why you get chest tightness when you're having an asthma attack. Here. we give male and female mast cells IL33, and we treat them with the P2X3 inhibitor. We see two things happening in my second graph. First, if we look at bars 1 and 3, we see that females are twice as responsive as males. And second, if we look at bars 1 and 2 versus 3 and 4, we see that females show a significant suppression of asthma-related cytokines when they're treated with the P2X3 inhibitor, compared to males that don't show any suppression at all. This supports my hypothesis that mast cell signalling may be worse in females due to the expression of the P2X3 receptor. To recap, it is known that IL 33, a muscle activator, can elicit inflammation on its own. But, my research is the first to show that IL 33 elicits an ATP release, acting on the P2X3 receptor hypothesized only to be present in females, creating a feed-forward loop, worsening inflammation in females than their male counterpart. My research is novel because it could explain why asthma is worse in females and also provides a therapeutic new target, P2X3, for developing drugs and blocking mast cell inflammation and finding a new cure for asthma and allergies. Thank you.

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