2023-12-21 19:17:11
The speech by Francesco Colucci, Professor of Immunology at the University of Cambridge, England
A book recently published by a Scottish ex-journalist midwife tells us about the mysteries and extraordinary biology of the uterus, where life begins. The story that I am telling you here is linked to the genetics of immunology. Did you know that natural killer cells in the womb help the fetus grow healthily? Life doesn’t get off to a great start for ten million newborns a year who don’t realize their growth potential. Born too young, these children are more likely to develop neurological disorders, cardiovascular disease, or diabetes as adults. There are various causes of reduced fetal growth, some linked to the malfunctioning of the placenta. The placenta is a vital organ that serves as the fetus’s lungs, liver, kidneys, and intestines. The placenta develops in the maternal womb in the first weeks of gestation, thanks to the cells of the mother’s immune system, led by the natural killer cells which, despite their name, do not kill but help to restructure the internal tissues of the maternal womb and their arteries that nourish the fetus until birth.
The natural killers that circulate in the blood are real killers. By killing other cells infected with viruses or cancer cells, they defend us from infections and tumors, together with other white blood cells. It does much more for our immune system than just belligerently defend us. A mass of over half a kilo of immune cells placed in every nook and cranny of the body, in the skin, lungs, intestines, liver and uterus, work day and night to keep us healthy with delicate and important peaceful operations.
For example, the internal covering of the uterus, which is capable of supporting a new life, is destroyed and regenerated every month four hundred times in the life of a woman aged from fifteen to fifty. Natural killer cells are among the most numerous in the uterus and participate in both the cycle and pregnancy. Our research has shown that natural killers in the uterus engage in intense molecular conversations with both maternal and fetal cells and together restructure local arteries to meet the growth needs of the fetus.
But be careful: before acting, both the pacifist natural killer cells of the uterus and the bellicose natural killer cells of the blood must obtain a license. One to reshape the pregnant uterus, the other to murder and defend ourselves. To obtain a license, natural killers must educate themselves. Thanks to their cell surface sensors, natural killers educate themselves by learning molecular codes of personal identity known as major compatibility genes, inherited from our parents and displayed on the cells of our body. Apart from identical twins who have identical codes, each has their own, individual and unique codes, different from the others. These codes mark the molecular individuality not only of all of us and our ancestors, but also of all animals living or having lived since the time of the big bang of genetics and immunology, that is, five hundred million years ago. Some codes are very ancient, they were already there in the time of the dinosaurs and are possessed by sharks, crocodiles, birds, and mammals, including laboratory mice. Others are recent and belong exclusively to humans and our close relatives chimpanzees and bonobos. We humans use both to educate natural killers and are divided into those who are genetically programmed to better use ancient codes and those who are modern codes. Natural blood killers educated by ancient codes work better in certain laboratory situations. These ancient codes are very similar between humans and laboratory mice and also regulate responses to modern viruses, including HIV and coronavirus.
In my laboratory in Cambridge, we have discovered that the ancient code is very important for the natural killers of the uterus of laboratory mice. And in fact, in mice that do not use this ancient code, the natural killers of the uterus do not participate correctly in the restructuring of the maternal womb. Less blood goes to fetuses and as a result malnourished ones do not realize their growth potential, with the brain not developing normally. We also found that among pregnant women, those genetically programmed not to use the ancient code are more likely to develop pre-eclampsia, a disorder that affects one in twenty pregnancies and is associated with reduced fetal growth. Until an artificial womb is able to conceive a human and ensure their health in adulthood, maternal natural killers, educated and pacifist, will continue to do their best to prepare us for life.
The precise mechanisms are part of the black box of reproductive biology. Research in this field could reveal them and help millions of children a year in the future. But not funded enough; what a serious mistake and what ingratitude towards these extraordinary cells!
Francesco Colucci, Professor of Immunology at the University of Cambridge, England
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December 21, 2023 (modified December 21, 2023 | 6:16 pm)
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