study uncovers genetic links to asthma inflammation, suggesting targeted therapy potential
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thanks to a new pathway discovery, personalized asthma therapies are closer than ever.
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a new study published in the journal proceedings of the national academy of sciences and conducted by medical researchers at chiba university japan has found gene region enhancers that act as a “key player in asthma-associated inflammation.”
the study found that the mice version of the human g900 region gene enhancers are closely related to inflammatory pathways.
with the results identifying new inflammatory pathways in asthma and giving more insight into how these pathways work, researchers are getting closer to creating new personalized and effective therapies for those living with inflammatory asthma.
asthma and inflammation
asthma is a chronic inflammatory condition driven by an immune response when a person is around specific triggers. inflammatory or allergic asthma, which is one of two types of asthma, is driven by an allergic reaction in the body that drives swelling of the airways, which leads to narrowing and tightening of the airway muscles.
when someone with inflammatory asthma comes into contact with an allergen, the immune system releases immunoglobulin e (ige), an antibody that encourages inflammation in an effort to neutralize the threat. there are various allergic asthma triggers, including:
- dust mites
- moulds
- pollen
- animals and pet dander
- food allergies or additives
- cockroaches
- other allergens
during the inflammatory process driven by the immune system, various pathways are involved, leading to the release of specific proteins, including type-2 cytokines by type-2 helper t (th2) cells and group-2 innate lymphoid cells (ilc2s).
for these cells to mature, they need high amounts of another protein, known as gata-binding protein 3 (gata3). these gene sequences, called enhancers, elevate the expression of gata3 in humans. the expression of genes is essentially the on/off switch that fosters or hinders specific physiological responses. in the study, the gata3 gene enhancers were shown to play a crucial role in the inflammatory pathways of asthma.
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the study breakdown
in the study, researchers looked at how g900 region enhancers located near the gata3 gene influenced differentiation, which is when young, immature cells mature into their individual characteristics and function. the result showed that these enhancers encouraged th2 differentiation, leading to an enhanced allergic response.
the study was conducted using mice. researchers removed the g900 region in the genome of the mice, which the study referred to as “knockout mice.” in those that lacked the g900 region, responses to allergens that can set off inflammatory asthma attacks were reduced due to the suppression of th2.
“one aspect we elucidate in our study is the role of the murine g900 region in th2 differentiation and allergic airway inflammation,” said professor hiroshi nakajima, the lead researcher in the study, in a press release. “this region, homologous to the human g900 region associated with asthma, is shown to be essential for in vivo th2 cell differentiation and allergic responses, particularly in the context of house dust mite (hdm)-induced allergic airway inflammation. furthermore, we have demonstrated that this g900 region is crucial for optimizing the three-dimensional chromatin structure near gata3 in th2 cells.”
essentially, because the g900 region was no longer present, gata3 couldn’t trigger the action of th2, resulting in less inflammation in the body due to a lack of inflammatory response from the immune system.
results that pave the way for potential new therapies
while the study results have found a new pathway to look toward when developing targeted therapies for inflammatory asthma, there is still a lot of work to do to use the data in a tangible way that helps those living with the condition.
the next steps are finding ways to regulate the differentiation of th2 through the restriction of gata3 enhancers in the genome. this tweak may help to reduce allergic asthma by hindering the immune system’s ability to take action against allergens that trigger asthma.
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“by identifying and understanding critical genetic regions that regulate immune responses, such as the mg900 region, it may be possible to develop precision medicine approaches tailored to individual genetic profiles. this could lead to more effective and personalized treatments, reducing the incidence and severity of allergic reactions and improving the quality of life for individuals suffering from these conditions,” prof. nakajima added in the release.
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