The innate immune response represents an important natural process providing a critical line of defense against infection and cancer. Innate lymphoid cells (ILCs) play a key role in this early immune response. Researchers at the Institut Pasteur’s Innate Immunity Unit (Inserm U1223) examining how these cells develop have identified new ILC precursors. This discovery constitutes a revolution for specialists in the field and could have an impact on ILC-based human cell therapy.
ILCs are essential cellular actors in early “innate” immunity. They rapidly produce inflammatory cytokines, while B and T cells, which are involved in later “adaptive” immunity, use specific antigen receptors to respond. ILC reactivity is one of the initial events of immune response, becoming active within hours of encountering pathogens. They therefore help maintain the body’s first line of defense against infections (bacterial, viral, fungal), during allergic responses or in eliminating cancer.
A new model of ILC development
In order to understand how ILCs develop, Institut Pasteur researchers characterized the hematopoietic precursors of these cells (ILCPs) that originate in the bone marrow: “In the course of our work, we realized that the current model for ILC development was incorrect.” Scientists previously believed that ILCP development involved two clearly distinct branches: one generating “natural killers” (NK cells) and the other producing “helper-like” ILCs (ILC1, ILC2, ILC3). “We developed a new reporter mouse strain, which enabled us to re-examine the phenotype and function of ILCPs. We were thus able to identify new ILCP subsets that retain the ability to develop simultaneously into NK cells and helper ILCs”, explains James Di Santo, Head of the Innate Immunity Unit. These “multipotent” ILCPs therefore provide a single cellular source for the production of these diverse innate effector cells.
Progress for research and human cell therapy
“We propose a revised model of ILC differentiation that redefines the cell fate potential of ILCPs”, continues James Di Santo. This is an important step for researchers in this field as the model guides most current research on ILCs. By understanding the signals responsible for the survival and expansion of these newly defined ILCPs, it may be possible to devise methods to generate mature ILCs with a log-term goal to implement human ILC therapy for infectious and inflammatory diseases.
An Id2RFP Reporter Mouse Redefines Innate Lymphoid Cell Precursor Potentials, Immunity, March 26th, 2019
Wei Xu1,2,3,7, Dylan E. Cherrier1,2,4,7 , Sylvestre Chea2,5, Christian Vosshenrich1,2 , Nicolas Serafini1,2 , Maxime Petit2,4,5, Pentao Liu6 , Rachel Golub2,5 and James P. Di Santo1,2
1 Innate Immunity Unit, Institut Pasteur, Paris 75724, France
2 Inserm U1223, Institut Pasteur, Paris 75724, France
3 Department of Immunology, Shanghai Medical College, Fudan University, Shanghai, China
4 Paris Diderot University, Paris, France
5 Lymphopoiesis Unit, Institut Pasteur, Paris, France
6 Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
7 These authors contributed equally