Researchers from UC Riverside School of Medicine collaborated with researchers at the Weizmann Institute of Science in Israel and uncovered a new type of cell in the thymus which is responsible for the production and maturation of immune cells.
The findings are published in Nature in an article titled, “Thymic mimetic cells function beyond self-tolerance.”
“Development of immunocompetent T cells in the thymus is required for effective defense against all types of pathogens, including viruses, bacteria, and fungi,” wrote the researchers. “To this end, T cells undergo a very strict educational program in the thymus, during which both non-functional and self-reactive T cell clones are eliminated by means of positive and negative selection. Thymic epithelial cells (TECs) have an indispensable role in these processes, and previous studies have shown the notable heterogeneity of these cells. Here, using multi-omic analysis, we provide further insights into the functional and developmental diversity of TECs in mice, and reveal a detailed atlas of the TEC compartment according to cell transcriptional states and chromatin landscapes.”
Professor David Lo, MD, PhD, and his graduate student Diana Del Castillo were consulted by researchers in Israel for their expertise on specialized cells called Microfold cells, or M cells, which are mostly known for their presence in the intestinal epithelium. The Israeli group had identified similar cells in the thymus.
Lo and Del Castillo, who are co-authors of the research paper published in Nature, confirmed the newly discovered cells in the thymus are just like M cells. Acting like gatekeepers, M cells are specialized antigen-delivery cells for the immune system in organs like the intestine and lung.
The researchers at the Weizmann Institute of Science in Israel, led by Jakub Abramson, PhD, initiated the mouse study on the thymic epithelium before contacting Lo, whose research interests include understanding how M cells in the gut and airways work to build our immune system.
“I have been working on these cells for several years, so when the Israeli team contacted me, I was intrigued,” Lo said. “I learned this group had been doing studies on the cellular architecture of stromal cells in the thymus and, using a new advanced method, had discovered a population of cells much like the M cells we see in the gut and airways. In my own research, I had simply never thought to look for M cells in the thymus.”
“These particular M cells are limited to a specific region in the thymus and have unique associations with different cell types and functions,” Del Castillo said. “Questions these cells have already prompted include how similar are they to M cells elsewhere in the body and what is different about where they have been found.”
Lo explained that for many years the thymus has been a tissue of interest to immunologists because most of the immune system’s development is centered and dependent on the thymus.
“It’s still an ongoing deep puzzle that continues to attract interest,” he said. “The thymus offers clues to how the immune system got its start. This complicated organ, with so many different stromal cell types and interactions, is responsible for producing lymphocytes that protect us from infection.”
The researchers found, however, that the thymic M cells have different developmental origins. “After they develop, they look very much like the ones we have been studying in the gut. As we know, M cells capture viruses and bugs that enter the airways and hand them off to the immune system, which then responds to the infectious agents. Are the M cells doing the same thing in the thymus in terms of organization and function? That’s what we would like to know.”
“We found the new cells were scattered in the medullary region of the thymus,” Del Castillo said. “This has interesting implications in terms of the role and compartmentalization of the thymus, such as how these cells may function to regulate lymphocyte training within this organ.”
“It is fascinating to see that many of these early cell interactions and development we have studied closely in the peripheral immune system take place in the thymus,” Lo said. “We had not anticipated to see these interactions here. It’s like watching a short video in the thymus about what is happening big-scale out in the periphery.”
“The newly discovered M cells are part of this decision-making process,” Del Castillo said. “The production of antibodies in the peripheral immune system to fight off infectious organisms involves several steps and many cells interacting with each other. What is fascinating is that some of these interactions are recapitulated in the early stages of the development of the thymic M cells.”
These new findings may lead to new approaches to studying the immune system and may lead to novel therapeutics.