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Date of Award
Doctor of Philosophy (PhD)
Group 1 ILCs produce IFN-g, express the T-box transcription factors (TFs) Eomes
and/or T-bet, and are positive for the cytotoxicity receptors NK1.1 and NKp46. This
population is composed of at least two cell types, NK cells and ILC1, which are
distinguished by their developmental origins and requirements. The mouse salivary
glands (SG) contain a large population of NK1.1 + cells which are IL-15 dependent but
only minimally produce IFN-g. Our studies reveal that NK1.1 + cells in the SG represent
a novel population of tissue resident Eomes + ILC1 (Chapter 2). SG ILC1 expressed
markers indicative of tissue residency and have alternative functionality through the
expression of the death inducing ligand TRAIL as well as CD39 and CD73 which can
generate adenosine from ATP. SG ILC1 had distinct requirements for the TFs NFIL3,
Eomes, and T-bet compared to both NK cells and Eomes - ILC1. Whole genome
microarray confirmed that SG ILC1 were a separate population in addition to revealing
that they expressed genes found in both NK cells and Eomes - ILC1.
We also found that the distinguishing properties of SG ILC1 were dependent on TGF-b
(Chapter 3). Loss of TGF-b signaling resulted in SG ILC1 becoming phenotypically and
functionally similar to NK cells while TGF-b exposure caused NK cells to upregulate SG
ILC1 markers. Mechanistically TGF-b repressed the expression of Eomes which acted
to promote NK cell markers and limit TGF-b imprinting. TGF-b acted through a non-
canonical Smad4-independent pathway which partially depended on JNK signaling.
TGF-b mediated SG ILC1 differentiation occurred in an age dependent manner which
mirrored SG development. Human SG also harbor a cell population which express
markers reminiscent of mouse SG ILC1. Taken together, these studies have expanded
the group 1 ILC family to include the TGF-b imprinted, Eomes + SG ILC1.
Chair and Committee
Wayne Yokoyama, Thad Stappenbeck, Tony French, Gene Oltz,
Cortez, Victor Samuel, "Characterization of Salivary Gland Innate Lymphoid Cells" (2016). Arts & Sciences Electronic Theses and Dissertations. 740.
Available for download on Friday, May 15, 2116