The Ohio State University
Human Innate Lymphoid Cell Biology and Development.
Degree: PhD, Biomedical Sciences, 2019, The Ohio State University
Studies of human lymphopoiesis are important towards
gaining a thorough understanding of normal immune cells and can
provide insights into the pathophysiology of immune disorders and
deficiencies. Innate lymphoid cells (ILCs) are a newly discovered
family of immune cells with emerging roles in the defense against
cancer, viral and bacterial infections, allergies, and autoimmune
diseases. These immune cells are unique in that they share features
of both innate and adaptive immunity. While ILCs lack the ability
to respond in an antigen-specific manner, they closely resemble
adaptive lymphocytes in terms of transcriptional signatures and
effector function. There are four types of ILCs: cytotoxic natural
killer (NK) cells and as many as three subsets of non-cytotoxic,
cytokine-producing “helper” ILCs termed ILC1s, ILC2s, and ILC3s
(the existence of ILC1s in states of normal human physiology
remains controversial). Currently, little is known about the
development and regulation of helper ILCs. Previously, our
laboratory discovered a comprehensive pathway of human NK cell
development in secondary lymphoid tissues (SLTs) such as tonsils
and lymph nodes exclusive of other ILCs, and have begun to explore
human ILC development in general. In particular, we and others have
described and characterized multipotent CD34+CD117- progenitor
cells as well as CD34+CD117+ common ILC progenitors in human
tonsils. Based on these data, we hypothesized that in humans all
ILCs share a common developmental pathway in tonsils and that at
some point, each ILC subset terminally differentiates along its own
developmental trajectory. Here we elucidated key steps of NK cell,
ILC2, and ILC3 development within human tonsils using ex vivo
molecular, transcriptional, and functional profiling and lineage
differentiation assays. We demonstrated that while tonsillar NK
cells, ILC2s, and ILC3s originate from a common ILC precursor cell
identified as CD34-CD117+, final steps of ILC2 development deviate
independently and become mutually exclusive from those of NK cells
and ILC3s, whose developmental pathways overlap. Moreover, we
discovered a CD34-CD117+ ILC precursor population that expresses
CD56 and gives rise to NK cells and ILC3s but not to ILC2s.
Collectively, our data support a comprehensive model for human ILC
development in tonsils, advancing our understanding of basic ILC
biology within the human immune system. Importantly, elucidating
these fundamental developmental pathways have enabled us to gain
greater insight into how cancer cells can disrupt ILC development
and function to further disease progression.
Advisors/Committee Members: Caligiuri, Michael (Advisor), Freud, Aharon (Advisor).
Subjects/Keywords: Immunology; Biomedical Research; Human innate lymphoid cells; ILC development; natural killer cells; cancer
to Zotero / EndNote / Reference
APA (6th Edition):
Chen, L. (2019). Human Innate Lymphoid Cell Biology and Development. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1551901769401192
Chicago Manual of Style (16th Edition):
Chen, Luxi. “Human Innate Lymphoid Cell Biology and Development.” 2019. Doctoral Dissertation, The Ohio State University. Accessed September 19, 2019.
MLA Handbook (7th Edition):
Chen, Luxi. “Human Innate Lymphoid Cell Biology and Development.” 2019. Web. 19 Sep 2019.
Chen L. Human Innate Lymphoid Cell Biology and Development. [Internet] [Doctoral dissertation]. The Ohio State University; 2019. [cited 2019 Sep 19].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1551901769401192.
Council of Science Editors:
Chen L. Human Innate Lymphoid Cell Biology and Development. [Doctoral Dissertation]. The Ohio State University; 2019. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1551901769401192