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with ILCs (green), epithelial
cells (red), and nuclei (blue)
University of Pennsylvania
Scientists say they’ve discovered the progenitors of innate lymphoid cells (ILCs) in the liver of fetal mice and the bone marrow of adult mice.
ILCs are among the first components of the immune system to confront certain pathogens, yet the cells went undetected by researchers for a century.
“Scientists tend to look for immune cells in the blood, lymph nodes, or spleen,” said Albert Bendelac, PhD, of the University of Chicago in Illinois.
“That is precisely where you would not find these cells. Once they mature, they directly go to tissues, such as the gut or the skin. You seldom see them in blood.”
To understand how ILCs fit into the ecosystem of cells that fight off infections and cancers, Dr Bendelac’s team focused on finding ILCs’ source.
And they reported their findings in a letter to Nature.
The team noted that ILCs, which were first recognized 5 years ago, are rare. A mouse might have 200 million lymphocytes and only a few thousand ILCs.
But previous work on natural killer (NK) cells showed that ILCs express the transcription factor PLZF during their development.
So Dr Bendelac and his colleagues created mice with the gene for green fluorescent protein inserted into mouse DNA, just downstream from the PLZF gene. As a result, cells from mice that expressed PLZF appeared bright green under the microscope.
Nevertheless, finding the precursors to ILCs was not easy. The precursors are not in the blood, and, by the time they migrate to the lungs or gut, they have already matured into ILCs.
The researchers eventually found the precursor cells—known as ILCPs—in the liver of fetal mice and in the bone marrow of adult mice.
When the team purified the ILCPs, which still contained the GFP gene, and transferred them into mice that lacked ILCs, the precursors were able to reconstitute the 3 known types of ILCs—ILCs 1, 2, and 3.
“There were no B cells or T cells or myeloid cells—no other immune cells, just these,” Dr Bendelac said. “So we think the ILCP really is a committed precursor to innate lymphoid cells.”
To confirm their finding, the researchers designed mice in which PLZF gene expression was tied to the gene for diphtheria toxin. When the cells expressed PLZF, they also produced the toxin, which was lethal for those cells. The result was a mouse that had a normal immune system except that it completely lacked ILCs.
“ILCs are found in the most exposed tissues,” Dr Bendelac noted. “They are one of your first lines of defense. We now suspect they may also influence the ensuing adaptive immune response, priming the pump, influencing how T-helper cells respond.”
Each of the 3 types of ILCs has different properties and serves different functions. ILC1 cells help prevent viral infections and can detect and remove some cancerous cells. They are similar to NK cells, except that NK cells circulate in the blood, and ILC1s live in the gut and the liver.
ILC2s are found in the lungs, where they can detect and respond to parasites. But they can also initiate an allergic reaction and mucus hyper-secretion.
ILC3 cells cluster in the gut, where they help mediate interactions between the bowel and bacteria. When that balance is disturbed, they can accelerate inflammation and may play a role in inflammatory bowel disease.
Dr Bendelac said his group’s research provides “one more tool for understanding this complex system,” and it could help generate a “powerful new way to assess the function of innate lymphocytes.” 
with ILCs (green), epithelial
cells (red), and nuclei (blue)
University of Pennsylvania
Scientists say they’ve discovered the progenitors of innate lymphoid cells (ILCs) in the liver of fetal mice and the bone marrow of adult mice.
ILCs are among the first components of the immune system to confront certain pathogens, yet the cells went undetected by researchers for a century.
“Scientists tend to look for immune cells in the blood, lymph nodes, or spleen,” said Albert Bendelac, PhD, of the University of Chicago in Illinois.
“That is precisely where you would not find these cells. Once they mature, they directly go to tissues, such as the gut or the skin. You seldom see them in blood.”
To understand how ILCs fit into the ecosystem of cells that fight off infections and cancers, Dr Bendelac’s team focused on finding ILCs’ source.
And they reported their findings in a letter to Nature.
The team noted that ILCs, which were first recognized 5 years ago, are rare. A mouse might have 200 million lymphocytes and only a few thousand ILCs.
But previous work on natural killer (NK) cells showed that ILCs express the transcription factor PLZF during their development.
So Dr Bendelac and his colleagues created mice with the gene for green fluorescent protein inserted into mouse DNA, just downstream from the PLZF gene. As a result, cells from mice that expressed PLZF appeared bright green under the microscope.
Nevertheless, finding the precursors to ILCs was not easy. The precursors are not in the blood, and, by the time they migrate to the lungs or gut, they have already matured into ILCs.
The researchers eventually found the precursor cells—known as ILCPs—in the liver of fetal mice and in the bone marrow of adult mice.
When the team purified the ILCPs, which still contained the GFP gene, and transferred them into mice that lacked ILCs, the precursors were able to reconstitute the 3 known types of ILCs—ILCs 1, 2, and 3.
“There were no B cells or T cells or myeloid cells—no other immune cells, just these,” Dr Bendelac said. “So we think the ILCP really is a committed precursor to innate lymphoid cells.”
To confirm their finding, the researchers designed mice in which PLZF gene expression was tied to the gene for diphtheria toxin. When the cells expressed PLZF, they also produced the toxin, which was lethal for those cells. The result was a mouse that had a normal immune system except that it completely lacked ILCs.
“ILCs are found in the most exposed tissues,” Dr Bendelac noted. “They are one of your first lines of defense. We now suspect they may also influence the ensuing adaptive immune response, priming the pump, influencing how T-helper cells respond.”
Each of the 3 types of ILCs has different properties and serves different functions. ILC1 cells help prevent viral infections and can detect and remove some cancerous cells. They are similar to NK cells, except that NK cells circulate in the blood, and ILC1s live in the gut and the liver.
ILC2s are found in the lungs, where they can detect and respond to parasites. But they can also initiate an allergic reaction and mucus hyper-secretion.
ILC3 cells cluster in the gut, where they help mediate interactions between the bowel and bacteria. When that balance is disturbed, they can accelerate inflammation and may play a role in inflammatory bowel disease.
Dr Bendelac said his group’s research provides “one more tool for understanding this complex system,” and it could help generate a “powerful new way to assess the function of innate lymphocytes.”
with ILCs (green), epithelial
cells (red), and nuclei (blue)
University of Pennsylvania
Scientists say they’ve discovered the progenitors of innate lymphoid cells (ILCs) in the liver of fetal mice and the bone marrow of adult mice.
ILCs are among the first components of the immune system to confront certain pathogens, yet the cells went undetected by researchers for a century.
“Scientists tend to look for immune cells in the blood, lymph nodes, or spleen,” said Albert Bendelac, PhD, of the University of Chicago in Illinois.
“That is precisely where you would not find these cells. Once they mature, they directly go to tissues, such as the gut or the skin. You seldom see them in blood.”
To understand how ILCs fit into the ecosystem of cells that fight off infections and cancers, Dr Bendelac’s team focused on finding ILCs’ source.
And they reported their findings in a letter to Nature.
The team noted that ILCs, which were first recognized 5 years ago, are rare. A mouse might have 200 million lymphocytes and only a few thousand ILCs.
But previous work on natural killer (NK) cells showed that ILCs express the transcription factor PLZF during their development.
So Dr Bendelac and his colleagues created mice with the gene for green fluorescent protein inserted into mouse DNA, just downstream from the PLZF gene. As a result, cells from mice that expressed PLZF appeared bright green under the microscope.
Nevertheless, finding the precursors to ILCs was not easy. The precursors are not in the blood, and, by the time they migrate to the lungs or gut, they have already matured into ILCs.
The researchers eventually found the precursor cells—known as ILCPs—in the liver of fetal mice and in the bone marrow of adult mice.
When the team purified the ILCPs, which still contained the GFP gene, and transferred them into mice that lacked ILCs, the precursors were able to reconstitute the 3 known types of ILCs—ILCs 1, 2, and 3.
“There were no B cells or T cells or myeloid cells—no other immune cells, just these,” Dr Bendelac said. “So we think the ILCP really is a committed precursor to innate lymphoid cells.”
To confirm their finding, the researchers designed mice in which PLZF gene expression was tied to the gene for diphtheria toxin. When the cells expressed PLZF, they also produced the toxin, which was lethal for those cells. The result was a mouse that had a normal immune system except that it completely lacked ILCs.
“ILCs are found in the most exposed tissues,” Dr Bendelac noted. “They are one of your first lines of defense. We now suspect they may also influence the ensuing adaptive immune response, priming the pump, influencing how T-helper cells respond.”
Each of the 3 types of ILCs has different properties and serves different functions. ILC1 cells help prevent viral infections and can detect and remove some cancerous cells. They are similar to NK cells, except that NK cells circulate in the blood, and ILC1s live in the gut and the liver.
ILC2s are found in the lungs, where they can detect and respond to parasites. But they can also initiate an allergic reaction and mucus hyper-secretion.
ILC3 cells cluster in the gut, where they help mediate interactions between the bowel and bacteria. When that balance is disturbed, they can accelerate inflammation and may play a role in inflammatory bowel disease.
Dr Bendelac said his group’s research provides “one more tool for understanding this complex system,” and it could help generate a “powerful new way to assess the function of innate lymphocytes.”