Date of Award
Doctor of Philosophy (PhD)
Transcriptional control of gene expression is essential for life, tailoring protein production to development and environment to maintain organismal homeostasis. A limited set of proteins termed transcription factors are critical to this process. As our understanding of these central regulators has improved, new aspects of cell and organismal biology have been revealed. Herein, we demonstrate the importance of the transcription factor Bhlhe40 to tissue-resident macrophages, T helper type 2 cells, and type 2 immune responses, revealing novel transcriptional control of macrophages and unexpected cytokine regulation of helminth infection. We find that Bhlhe40 is cell-intrinsically required for normal proliferation of large serous cavity macrophages, but not other tissue-resident macrophage populations, revealing tissue-specific control of macrophage cycling active in homeostasis and type 2 immunity. Furthermore, we demonstrate that Bhlhe40 is critical for a normal transcription response of T helper cells to secondary infection with the helminth Heligmosomoides polygyrus bakeri (H. polygyrus). T cell-intrinsic loss of Bhlhe40 impairs protective memory to H. polygyrus and reveals novel redundancy between the common beta chain-dependent cytokines GM-CSF and IL-5 in anti-helminth immunity.
Chair and Committee
Brian T. Edelson
Paul M. Allen, Marco Colonna, Gwendalyn J. Randolph, Thaddeus S. Stappenbeck,
Jarjour, Nicholas N., "The Transcription Factor Bhlhe40 Regulates Tissue-Resident Macrophages and Type 2 Immunity" (2019). Arts & Sciences Electronic Theses and Dissertations. 2004.