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Human Innate Lymphoid Cell Development

Scoville, Steven
http://orcid.org/0000-0003-1597-1267
http://rave.ohiolink.edu/etdc/view?acc_num=osu1459952541

Abstract Details

2016, Doctor of Philosophy, Ohio State University, Biomedical Sciences.
Innate lymphoid cells (ILC) were recently discovered as a novel subset of the immune system. While typical adaptive lymphocytes, such as B and T cells, respond in an antigen specific manner, ILCs are distinct in that they lack the gene-rearrangement events necessary to elicit antigen specific responses. Nonetheless, through their unique functional profile ILCs play a vital role in promoting overall health by eliminating certain types of viruses, bacteria, worms, and even cancer cells. In fact, some evidence suggests that cancer cells actively suppress ILCs. ILCs are divided into four distinct populations known as natural killer (NK) cells, ILC1, ILC2 and ILC3, each displaying unique transcriptional and functional effector profiles. They are also found in many different physiological locations, but they are collectively enriched within secondary lymphoid tissues (SLT), such as tonsils and lymph nodes. However, how and where human ILCs develop is currently not known. We hypothesized that ILCs develop from progenitors found in SLT. Our lab previously showed that a distinct population of CD34(+)CD45RA(+) lymphoid progenitors exists in SLTs. Dissecting these progenitors with respect to surface markers commonly found on mature ILC subsets, we discovered a novel progenitor population, identified as CD34(+)CD45RA(+)ID2(+)CD117(+)IL-1R1(+)ROR¿t(+), that is only found in SLT locations such as human tonsils, lymph nodes, and spleen, but not in non-SLT hematopoietic locations such as peripheral blood, cord blood, thymus, and bone marrow. A hallmark of progenitor differentiation is the distinct loss of multi-lineage potential, thus we performed in vitro differentiation assays to determine the lineage restriction of this novel population. Remarkably, the ID2(+)CD117(+)IL-1R1(+) subset we identified was not capable of developing into T cells or dendritic cells, despite being in conditions that promoted the differentiation of those lineages from other SLT progenitor subsets. However, this population was capable of differentiating into all ILC populations as tested in vitro even at the clonal level. Furthermore, subsequent work has also demonstrated that this cell selectively gives rise only to ILCs in vivo, after injecting these cells into an immunodeficient mouse. In conclusion, we are the first to identify and characterize a progenitor population in humans that is only capable of ILC development and no other lymphocyte lineage. These findings are now being used to help us understand how cancer cells work to suppress the development and function of ILCs to promote disease progression. More importantly, our findings provide new targets that may be helpful in overcoming this effect and may be useful in cancer therapy.
Michael Caligiuri (Advisor)
132 p.
Immunology
cancer; innate lymphoid cells; NK cells; development

Recommended Citations

Citations

  • Scoville, S. (2016). Human Innate Lymphoid Cell Development [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1459952541

    APA Style (7th edition)

  • Scoville, Steven. Human Innate Lymphoid Cell Development. 2016. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1459952541.

    MLA Style (8th edition)

  • Scoville, Steven. "Human Innate Lymphoid Cell Development." Doctoral dissertation, Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1459952541

    Chicago Manual of Style (17th edition)

osu1459952541
245
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This open access ETD is published by The Ohio State University and OhioLINK.