Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 50, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2117965118
Keywords
innate lymphoid cells; natural killer cells; Hobit; Eomes; liver
Categories
Funding
- NCI Cancer Center Support Grant [P30 CA91842]
- National Center for Research Resources (NCRR) [UL1TR002345]
- NIH [R01 AI130152]
- Child Health Research Center K12
- Rheumatology Research Foundation Tobe and Stephen E. Malawista, MD Endowment in Academic Rheumatology
- [U01 AI095542]
- [R01 DE025884]
- [R01 AI134035]
- [R01 DK124699]
- [U19 AI142733]
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The study found that the expression of Hobit/Zfp683 is correlated with ILC1s and NK cells in a tissue- and context-dependent manner, with different effects on ILC1s and NK cells in different tissues. Hobit sustains liver ILC1 numbers while promoting the functional maturation of ILC1 in other tissues.
Identification of type 1 innate lymphoid cells (ILC1s) has been problematic. The transcription factor Hobit encoded by Zfp683 has been proposed as a major driver of ILC1 programs. Using Zfp683 reporter mice, we showed that correlation of Hobit expression with ILC1s is tissue- and context-dependent. In liver and intestinal mucosa, Zfp683 expression correlated well with ILC1s; in salivary glands, Zfp683 was coexpressed with the natural killer (NK) master transcription factors Eomes and TCF1 in a unique cell population, which we call ILC1-like NK cells; during viral infection, Zfp683 was induced in conventional NK cells of spleen and liver. The impact of Zfp683 deletion on ILC1s and NK cells was also multifaceted, including a marked decrease in granzyme- and interferon-gamma (IFN gamma)-producing ILC1s in the liver, slightly fewer ILC1s and more Eomes(+) TCF1(+) ILC1-like NK cells in salivary glands, and only reduced production of granzyme B by ILC1 in the intestinal mucosa. NK cell-mediated control of viral infection was unaffected. We conclude that Hobit has two major impacts on ILC1s: It sustains liver ILC1 numbers, while promoting ILC1 functional maturation in other tissues by controlling TCF1, Eomes, and granzyme expression.
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