Th165 - TCR Gene Rearrangements and a Novel Fate Mapping Mouse as Tools for Studying the Origins Fate of Innate Lymphoid Cells

Ahmed Kabil – Graduate Student, School for Biomedical Engineering, U of British Columbia; Samuel Shin – Graduate Student, School for Biomedical Engineering, U of British Columbia; Monica Romera-Hernandez, PhD – PDF, BC Cancer Agency, U of British Columbia; Michael Hughes, PhD – PDF, School for Biomedical Engineering, U of British Columbia; Yicong LI – technician, School for Biomedical Engineering, U of British Columbia; Taka Murakami – Technician, School for Biomedical Engineering, U of British Columbia; Julyanne Brassard, PhD – PDF, School for Biomedical Engineering, U of Britsh Columbia; Fumio Takei, PhD – Professor, BC Cancer Agency, U of British Columbia

Abstract Text: Innate lymphoid cells (ILCs) are a recently identified lineage of lymphocytes that play a central role in pathogen surveillance, modulation of immune response, and tissue repair. ILC1s, ILC2s and ILC3s show remarkable similarity to Th1, Th2 and Th17 T cells, respectively, in terms of their cytokine production, function and transcription factor dependence but have been regarded as thymic-independent due to their lack of expression of cell surface T cell receptor, their abundance in RAG-deficient mice and the identification of ILC precursor cells in the bone marrow. Recently, we made the striking observation that highly purified lung ILC2s, ILC3s and ILC precursors from normal adult mice exhibit frequent V-to-J gene segment rearrangements of TCR gamma chain loci and/or deletions of the TCR delta constant region locus consistent with failed T cell development within the thymus. These data challenge the bone marrow centric view of ILC development and instead argue for a thymic origin of some fraction of the tissue resident ILCs. Whether these thymic-derived ILCs represent an early developmental wave or a continued production of ILCs from the adult thymus remains an open question. To investigate this further, we have now generated a novel mouse strain (IL17Rb-CreERT2-IRES-GFP) that permits the highly-selective, vital, monitoring of all tissue ILC2s, and the pulse labeling of these cells for tracing their fate during development. The combine use of this novel, highly-selective, pulse-labeling strategy together with TCR gene rearrangements as a natural barcode now allows us to directly address ILC origins, fate and plasticity in tissues.