House dust mites abound across the world. Cleaning will very certainly cause some to erupt. While everyone’s immune cells are capable of reacting to common allergens such as house dust mites, the majority of us do not experience allergic symptoms.
Even yet, many people have the classic allergy symptoms of sneezing, runny nose, and itchy, swollen nasal passages. Others have a much more severe reaction: an asthma attack that can be fatal.
To treat the underlying causes of allergies and asthma, researchers must first understand what distinguishes these patients from healthy people.
Scientists at the La Jolla Institute for Immunology (LJI) offer a clue as to why non-allergic persons don’t have a severe reaction to house dust mites in a new Science Immunology article published on June 12, 2020.
They discovered a previously unknown subset of T cells that could prevent allergic immune reactions and asthma from developing in response to house dust mites and other allergens.
“We discovered new immune cell subsets and new therapeutic opportunities,” says Grégory Seumois, Ph.D., instructor and director of LJI’s Sequencing Core and co-leader of the new study. “This new population of cells could be one, out of many unknown mechanisms, that explains why healthy people don’t develop inflammation when they breathe in allergens.”
“The study highlights the power of unbiased single-cell genomics approaches to uncover novel biology,” says LJI Professor Pandurangan Vijayanand, M.D. Ph.D., senior author of the new study.
We discovered new immune cell subsets and new therapeutic opportunities. This new population of cells could be one, out of many unknown mechanisms, that explains why healthy people don’t develop inflammation when they breathe in allergens.
Grégory Seumois
The research expands on the Vijayanand lab’s experience in tying gene expression to illness progression. The team also used the Immune Epitope Database, a resource run by the LJI that contains data on how the immune system interacts with allergens such as house dust mites.
Why house dust mites?
Because these minuscule organisms are difficult to avoid, practically everyone has been exposed. Even in persons who aren’t allergic to house dust mites (HDMs), the immune system will react in some way as it learns to recognize HDM molecules.
As a result, HDM can be used to research what causes allergies and asthma attacks. To discover exactly which genes and chemicals specific T cells produce in response to HDM allergens, the LJI team employed single-cell RNA-seq (or single cell transcriptomics), a technology from the “genomic revolution” arsenal of tools.
Persons with asthma and HDM allergy, people with asthma but no HDM allergy, people with only HDM allergy, and healthy volunteers were all tested.
Their findings imply that in patients with HDM-allergic asthma, a subset of helper T cells known as interleukin (IL)-9 Th2 expressing HDM-reactive cells is more frequent in the blood than in people who are only allergic to HDM.
Further research revealed that those IL9-TH2 cells are high in a collection of molecules/genes that boost their cytotoxic ability. To put it another way, those specific T cells have the potential to kill other cells and cause inflammation.
In the non-allergic participants, however, another population of T cells stood out. These T cells had a “interferon response signature” and were found to be high in a gene that codes for the protein TRAIL. According to Seumois and colleagues’ findings, TRAIL may be essential because it inhibits the activation of helper T cells.
This finding could indicate that people with this cell population are less likely to have T-cell-driven inflammation in response to HDM allergens. Finally, this may explain why some people acquire allergies and asthma while others do not.
“Now if functional studies confirm this dampening effect, we’re curious if there is a way to boost the activation of these T cells or induce their proliferation in asthmatic or allergic populations,” says Seumois.
“Can we act on those cells very early on, before asthma has developed?”
For example, genomics research like this one may one day aid in identifying children at risk of asthma and allergies. Early detection could pave the way for immune cells to be targeted before allergies and asthma develop.
While Seumois adds that much more research is needed, he believes that the transcriptomic method utilized in this study could help to speed up future asthma and allergy studies.
“This is the first large-scale, single-cell, RNA-seq transcriptomic analysis for LJI,” says Seumois. “Now that we have developed the bench know-how and analysis pipeline, it could be applied to many diseases.”
