1. What have you found so far?
Previous research has shown that retinoic acid (RA) is important for both initiating T cell responses to pathogens, as well as promoting tolerance in the gut. My research is looking at different mechanisms that are influenced by RA, and what we found was a novel transcription factor that is only expressed in T cells located in the small intestine or T cells that are treated with exogenous RA. Interestingly, when we knock this molecule out or inhibit it in T cells, we find that cytokine production is altered, and in doing so, we are able to prevent disease progression in different animal models of colitis.
2. Does this novel transcription factor differentially affect the various subsets of T cells?
We find that it has an affect on Th17 cells. When we inhibit this transcription factor, it seems to allow T cells to produce a lot more IL-17 and IL-10, so it seems to promote barrier functions and immunoregulatory molecules. We think that is how it is protecting from disease progression in colitis.
Lots of evidence in the literature show that IL-17 both has a pro-inflammatory and an anti-inflammatory effect. IL-17 is known to mediate protection from extracellular pathogens such as fungi, but it has also been shown to promote intestinal epithelial cells to have stronger, tighter junction and promote barrier function, so that bacterial cells cannot cross the epithelial surface and induce inflammation.
3. What do you consider to be the most significant advancement in the field in the last 5 years?
I think a very hot topic right now is innate lymphoid cells (ILCs). They were discovered not too long ago, about 5 years, and research with them has just exploded. They were originally discovered as a single subset, but now there are multiple subsets: ILC1s, ILC2s and ILC3s, and they have very different functions. ILC2s in the lung are very important for inducing airway inflammation in response to antigens. You have ILC3s that are important for microbial defenses as well as regulating responses against commensal bacteria. There is a lot of research focusing on ILCs right now, and it is only going to expand in the future.
4. What is the main technical challenge in the field?
I think the main technical challenge in the field right now is with the characterization of innate lymphoid cells, because they are such a rare population, they don't have a good marker, like T cell receptors on T cells, it is hard to identify these cells in vivo. It involves a lot of different antibodies and a lot of staining. I think there needs to be a new way to identify these cells. A tool like the CyTOF may help in the future once they start being more common in laboratories, but right now I would say we're pretty limited in our staining capabilities to identify these rare subsets.
It's quite difficult to isolate ILCs right now because they're so rare. If there was definitely a faster and easier way to sort ILCs, it would be a great advantage to my research. Especially because sorting takes so long, cells are usually sitting in the machine for a long time and you end up getting a lot of dead cells. A way to increase viability, say with magnetic sorting, would be definitely beneficial to research.
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