Recently, researchers in Israel turned to Professor David Lo and his graduate student Diana Del Castillo for their expertise in specialized cells called microfold cells, or M cells. The Israeli research team discovered similar cells in the thymus, an organ above the heart that makes lymphocytes -- white blood cells that play an important role in the immune system and protect the body from infection.
Image shows thymocytes (mouse model). The nuclei of all cells are dark blue, M cells are cyan, and B cells (lymphocytes) are red or red/green. Source: Lo Lab, University of California, Riverside
Luo and Del Castillo, distinguished professor of biomedical sciences at the University of California, Riverside School of Medicine, and co-authors of a study published in Nature, confirmed that the newly discovered cells in the thymus are identical to M cells. M cells are like gatekeepers, specialized antigen delivery cells of the immune system in organs such as the intestines and lungs. They play a key role in the development of the human immune system.
Researchers at the Weizmann Institute of Science in Israel, led by Jakub Abramson, initiated mouse studies of thymic epithelial cells before getting in touch with Lo, whose research interests include understanding how M cells in the gut and respiratory tract function to build our immune system.
"I had been studying these cells for several years, so when the Israeli team contacted me, I was intrigued," Lo said. "I learned that this research group had been studying the cellular structure of stromal cells (the cells that make up certain types of connective tissue) in the thymus and, using a new advanced method, discovered a cell population that was very similar to the M cells we see in the intestines and airways. In my own research, I had never thought of looking for M cells in the thymus."
Del-Castillo, under Luo's guidance, has been studying mucosal tissue in mice - the mucosal tissue that lines some of the body's tubes and organs - in the lab and was able to answer several questions, such as where in the thymus the newly discovered cells are located and what they do there.
Unique properties of thymic M cells
"These specialized M cells are localized to specific areas of the thymus and have unique associations with different cell types and functions," Del Castillo said. "These cells have raised questions, including how similar they are to M cells elsewhere in the body, and how they differ where they are found."
Lo explained that the thymus has been a tissue of interest to immunologists for many years because much of the development of the immune system is centered on and dependent on the thymus.
"This remains a deep mystery that continues to attract interest," he said. "The thymus provides clues about how the immune system gets started. This complex organ has many different stromal cell types and interactions responsible for producing the lymphocytes that protect us from infection."
According to Lo, the newly discovered M cells are very similar to those found in the intestines and respiratory tract.
"But thymic M cells have a different developmental origin, which is an interesting puzzle in itself. After development, they look very much like the M cells in the intestine that we have been studying. We know that M cells capture viruses and germs that enter the respiratory tract and hand them over to the immune system, which then responds to the infectious pathogens. Are M cells organized and functioning the same way in the thymus? That's what we wanted to know," he said.
Exploring the functions of thymic M cells
Del-Castillo, who is pursuing a PhD in biomedical sciences, used genetically engineered mice to address the questions posed by Israeli researchers.
"We found new cells scattered throughout the medullary region of the thymus," she said. "This has interesting implications for the role and compartmentalization of the thymus, such as how these cells might function to regulate lymphocyte training within this organ."
Lo and DelCastillo were surprised to find that many of the steps in building an immune response in various parts of the body seemed to echo the thymus.
"It's fascinating that many of the early cellular interactions and developmental processes we've studied carefully in the peripheral immune system occur in the thymus," Lo said. "We didn't expect to see these interactions here. It's like watching a short video in the thymus and understanding the big events going on in the periphery."
The thymus also ensures that lymphocytes don't accidentally attack our own tissues; the thymic medulla is where these decisions are made, UCR scientists say.
"The newly identified M cells are part of this decision-making process," Del-Castillo said. "The process by which the peripheral immune system produces antibodies to defend against infectious organisms involves multiple steps and interactions between many cells. Fascinatingly, some of these interactions are recapitulated in the early stages of thymic M cell development."
Lo believes that thymic M cells can be viewed as a kind of training to later function in the periphery when needed, allowing them to communicate and interact with other cells at any time.
He said: "The thymus is complex because it creates a complete functional immune system and immune repertoire, and we know that many of its components play a role in its performance. We did not expect M cells to be present in the thymus. So this is a satisfying finding because it is so clearly linked to similar processes that occur in the gut and airways, through which 60-70% of our infectious pathogens enter the body."
Compiled source: ScitechDaily