Researchers from the University of Chicago have identified progenitor cells that produce innate lymphoid cells (ILCs), a class of anti-infective leukocyte populations discovered in recent years, in the fetal liver and bone marrow of mice. The research results were published online in the journal Nature.
ILCs are one of the first-line components of the immune system against certain pathogens. They perform vital functions at sites where the body is in direct contact with the environment, such as the intestinal or lung mucosal barrier. However, scientists who have been studying the immune system for a century have not discovered them.
The author of the study, Dr. Albert Bendelac, a professor of pathology at the University of Chicago, said: "Scientists often look for immune cells in the blood, lymph nodes or spleen. And precisely where you will not find ILCs. Once mature, they will directly enter the intestine Skin and other tissues. You can hardly see them in the blood.
To understand where these cells originated and how they were incorporated into the cell ecosystem that fights infection and cancer, the Bendelac research team focused on finding the source of ILCs.
Congenital lymphocytes recognized by people only 5 years ago are very rare. A mouse may have 200 million lymphocytes, but only a few thousand ILCs. From previous research work on NKT cells, researchers learned that during the development of innate lymphocytes, they express an unusual transcription factor, PLZF. So they inserted the green fluorescent protein gene into the DNA downstream of the mouse PLZF gene to construct a "reporter" mouse. Therefore, cells from these mice that express PLZF will appear bright green under the microscope.
Although the green luminescent cells are very conspicuous, it is not easy to find the progenitor cells of these lymphocytes at a rate of 1 in 10,000. These progenitor cells do not exist in the blood, and when they migrate into the lungs or intestines, they have matured into ILCs. The researchers eventually found precursor cells of congenital lymphocytes (ILCPs) in the liver of fetal mice and the bone marrow of adult mice.
The researchers purified these ILC precursor cells and transferred them to mice lacking ILCs. These precursor cells were able to reconstruct three known types of innate lymphocytes. Bendelac said: "There are no B cells, T cells or myeloid cells, and no other immune cells are these cells. Therefore, we believe that ILCP is really a precursor precursor cell of innate lymphocytes.
To verify their findings, the researchers designed mice with PLZF gene expression linked to the diphtheria toxin gene. When cells express PLZF, they also produce toxins, which are lethal to these cells. As a result, the mouse has a normal immune system but it completely lacks innate lymphocytes.
Some recent studies have confirmed the importance of ILCs. They play a key role in fighting infections or parasites, but they are also associated with autoimmune diseases.
Three types of innate lymphocytes-ILCs 1, 2 and 3 have different characteristics and perform different functions. ILC1 helps prevent viral infections and can detect and remove some cancer cells. They are similar to natural killer (NK) cells, except that NK cells circulate in the blood and ILC1s are located in the intestine and liver. ILC2s are present in the lungs, where they can detect parasites and respond, but they can also trigger allergic reactions and excessive secretion of mucus. The accumulation of ILC3 cells in the intestine helps mediate the direct interaction between the intestine and bacteria. When the balance is broken, they promote inflammation and may play a role in inflammatory bowel disease.
Bendelac said: "" ILCs are found in most exposed tissues. They are one of your first lines of defense. We now suspect that they may affect the subsequent adaptive immune response and affect the helper T cell response.
Bendelac said: "Our results provide another tool for understanding this complex system. This will help generate powerful new methods to assess the function of innate lymphocytes."
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