Epigenetic control of innate lymphoid cell homeostasis and development / Walter Keith Mowel.

Format:

Book

Manuscript

Thesis/Dissertation

Author/Creator:

Mowel, Walter Keith, author.

Contributor:

Henao-Mejia, Jorge, degree supervisor.

Brodsky, Igor E., degree committee member.

Kambayashi, Taku, degree committee member.

Laufer, Terri M., degree committee member.

Wherry, E. John, degree committee member.

University of Pennsylvania. Department of Immunology, degree granting institution.

Language:

English

Subjects (All):

Penn dissertations--Immunology.

Immunology--Penn dissertations.

Local Subjects:

Penn dissertations--Immunology.

Immunology--Penn dissertations.

Physical Description:

xii, 174 leaves : illustrations (some color) ; 29 cm

Production:

[Philadelphia, Pennsylvania] : University of Pennsylvania, 2019.

Summary:

Commitment to the innate lymphoid cell (ILC) lineage is determined by Id2, a transcriptional regulator that antagonizes T and B cell-specific gene expression programs. Yet how Id2 expression is regulated in each ILC subset remains poorly understood. Emerging data suggests that epigenetic regulation by long non-coding RNAs (lncRNAs) plays a critical role in cell type-specific regulation of gene expression in immune cells. In this thesis, we identified a cis-regulatory element demarcated by a lncRNA that controls the function and lineage identity of group 1 ILCs, while being dispensable for early ILC development and homeostasis of ILC2s and ILC3s. The locus encoding this lncRNA, which we termed Rroid, directly interacted with the promoter of its neighboring gene, Id2, in group 1 ILCs. Moreover, the Rroid locus, but not the lncRNA itself, controlled the identity and function of ILC1s by promoting chromatin accessibility and deposition of STAT5 at the promoter of Id2 in response to interleukin (IL)-15. Furthermore, a second regulatory element, which we called Id2-DS3, regulated ILC2 levels by promoting their early development. Thus, this study suggests that non-coding elements responsive to extracellular cues unique to each ILC subset represent a key regulatory layer for controlling the identity and function of ILCs.

Notes:

Ph. D. University of Pennsylvania 2019.

Department: Immunology.

Supervisor: Jorge Henao-Mejia.

Includes bibliographical references.

Other Format:

Online version: Mowel, Walter Keith. Epigenetic control of innate lymphoid cell homeostasis and development.

OCLC:

1121630330