New cell type discovered in thymus

UC Riverside biomedical scientists say the cells are like M cells in the gut and airways.

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Microfold cells, or M cells, are usually found in the intestinal epithelium. A new study by Professor David Lo and his graduate student Diana Del Castillo reports the discovery of similar cells in the thymus. The organ Thymus is located just above the heart that makes lymphocytes.

The discovery surprised scientists when researchers in Israel recently consulted them for their expertise on specialized cells called M cells.

M cells act as gatekeepers for the immune system in organs like the intestine and lungs. They play a crucial role in delivering specialized antigen cells during the development of the body’s immune system.

In the mouse study on the thymic epithelium, researchers at the Weizmann Institute of Science in Israel wanted to determine the function of M cells in the gut and airways.

Lo said, “I learned this group had been doing studies on the cellular architecture of stromal cells — cells that make up certain types of connective tissue — 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 research, I had never thought to look for M cells in the thymus.”

thymic cells
Image shows thymic cells (mouse model). Nuclei of all cells present are dark blue, M cells are turquoise, and B cells (lymphocytes) are red or red/green. (UCR/Lo lab)​

Fortunately for the Israeli scientists, Del Castillo had been studying mucosal tissues in mice in the lab under Lo’s supervision. He had been able to provide answers to several questions, including where the newly discovered cells are located and what they are doing there. 

Del Castillo said, “These particular M cells are limited to a specific region in the thymus and have unique associations with different cell types and functions.”

“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. 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.”

According to Lo, the newly discovered M cells are extremely similar to those in the gut and airways. 

“But the thymic M cells have different developmental origins, which is an interesting puzzle in itself. After they develop, they look like the ones we have studied in the gut. As we know, M cells capture viruses and bugs that enter the airways and hand them off to the immune system, responding to the infectious agents. Are the M cells doing the same thing in the thymus regarding organization and function? That’s what we would like to know.”

Del Castillo, who is working toward her doctoral degree in biomedical sciences, used genetically engineered mice to tackle the questions from the Israeli researchers.

She said, “We found the new cells were scattered in the medullary region of the thymus. This has interesting implications regarding the role and compartmentalization of the thymus, such as how these cells may function to regulate lymphocyte training within this organ.”

Lo and Del Castillo were shocked to discover that the thymus seemed to mirror many of the procedures required to form an immune response in different body sections. It is fascinating that many of these early cell interactions and development we have studied closely in the peripheral immune system occur in the thymus.

Lo said, “We weren’t prepared for these interactions to occur here. It’s similar to watching a little video of major events taking place in the peripheral in the thymus.”

The thymus also controls whether cells unintentionally assault our own tissues; these decisions are determined in the thymic medulla.

Del Castillo said“The newly discovered M cells are part of this decision-making process. 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.”

Lo said, “The thymic M cells could be seen as being trained to function later, when needed, in the periphery so that they are ready to communicate and interact with other cells.”

“The thymus is complicated because it creates a whole functional immune system and repertoire, and we know many component parts play a role in its performance. We didn’t expect M cells to even show up in the thymus. This is, therefore, a satisfying discovery because it is so clearly connected to similar processes happening in the gut and airways, which is where 60-70% of our infectious agents enter our bodies.”

Journal Reference:

  1. Givony, T., Leshkowitz, D., Del Castillo, D. et al. Thymic mimetic cells function beyond self-tolerance. Nature (2023). DOI: 10.1038/s41586-023-06512-8
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