The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor

The mucus-covered tissues that line the nose, mouth, and the digestive tract play an important role in protecting the body from infection. These mucosal tissues are the first line of defense against any pathogens we inhale or ingest, and help to keep communities of helpful bacteria—such as those that aid digestion—in place so that they can perform their beneficial functions without causing disease. A special group of immune cells called innate lymphoid cells helps to prevent infection in the mucosal tissues and to repair damage to these tissues. There are several different types of innate lymphoid cells, with each type performing a different function. All innate lymphoid cells originate from precursor cells in the bone marrow. Some of these precursor cells had been identified previously, but were able to develop into only some of the different innate lymphoid cell types. Scientists suspected that a precursor cell existed that could develop into all types of innate lymphoid cell, but the identity of this cell had remained elusive. Yu, Wang et al. now identify a precursor cell in the bone marrow that can produce all of the currently known different types of innate lymphoid cells. A protein called NFIL3 coaxes stem cells in the bone marrow into becoming these precursor cells, which only develop into innate lymphoid cells, and not into other immune cell types such as B cells and T cells. Yu, Wang et al. find that NFIL3 causes some of these previously identified precursor cells to become dedicated producers of innate lymphoid cells by regulating another protein called TOX. Furthermore, gene therapy using NFIL3- or TOX-encoding DNA can help to restore normal numbers of innate lymphoid cells in mice whose bone marrow progenitor cells lack the NFIL3 gene. These new details about how bone marrow stem cells develop into innate lymphoid cells may help scientists looking for new ways to treat infections or diseases that hamper the innate immune system.