Location: Diet, Genomics and Immunology LaboratoryTitle: Down-regulation of E protein activity augments an ILC2 differentiation program in the thymus
|WANG, HONG-CHENG - Oklahoma Medical Research Foundation|
|ZHAO, YING - Oklahoma Medical Research Foundation|
|QIAN, MIRANDA - Oklahoma Medical Research Foundation|
|ADRIANTO, INDRA - Oklahoma Medical Research Foundation|
|MONTGOMERY, COURTNEY - Oklahoma Medical Research Foundation|
|FUNG, KAR-MING - University Of Oklahoma Health Sciences Center|
|SUN, XIAO-HONG - Oklahoma Medical Research Foundation|
Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/3/2017
Publication Date: 4/15/2017
Citation: Wang, H., Zhao, Y., Qian, M.L., Adrianto, I., Montgomery, C.G., Urban Jr, J.F., Fung, K., Sun, X. 2017. Downregulation of E protein activity augments an ILC2 differentiation program in the thymus. Journal of Immunology. 198(8):3149-3156. doi: 10.4049/jimmunol.1602009.
Interpretive Summary: Helminth (worm) infections are a global health concern in livestock, as well as humans, because they establish chronic and repeated infections. The characterization of immune cells that are part of the innate immune response, namely innate lymphoid cells (ILC) that are activated in a naive host not previously infected, has stimulated interest in how and where in the body that these cells are generated to populate mucosal surfaces that encounter pathogens. Rapid progress has led to the notion that ILCs originate from common lymphoid progenitors, and downstream ILC progenitors have been identified in the bone marrow. However, it is unclear if multipotent progenitors distinct from common lymphoid progenitors or those residing outside of the bone marrow can also produce ILCs. For example, some of these progenitors are shown to travel to the thymus where other lymphoid cells are “educated” to respond to external stimuli because of differentiation factors that are present there. Our findings showed specific down-regulation of an E protein in the thymus greatly expanded ILC2 production in the thymus. This information will inform scientists interested in developing useful and safe procedures to protect humans and livestock from parasitic infection and allergic disease.
Technical Abstract: Innate lymphoid cells (ILCs) are important regulators in various immune responses. Current paradigm states that all newly-made ILCs originate from common lymphoid progenitors (CLP) in the bone marrow. Id2, an inhibitor of E protein transcription factors, is indispensable for ILC differentiation. Unexpectedly, we found that specifically expressing Id1 or deleting two E protein genes in the thymus resulted in massive expansion of ILC2s in the thymus and other organs where ILC2 normally reside. Consequently, the mutant mice exhibit augmented spontaneous infiltration of eosinophils and heightened responses to allergens in the lung. Furthermore, these mice also display increased ability to expulse the helminth parasite, Nippostrongylus brasiliensis. These results thus prompt the question whether the thymus naturally has the capacity to produce ILC2s and E proteins restrain such a potential. The abundance of ILC2s in Id1 transgenic mice also offers a unique opportunity for testing the biological functions of ILC2s.