Hobit confers tissue-dependent programs to type 1 innate lymphoid cells

Area of Science:

• Immunology
• Cell Biology

Background:

• Type 1 innate lymphoid cells (ILC1s) are crucial immune cells, but their identification has been challenging.
• The transcription factor Hobit (encoded by Zfp683) has been implicated as a key regulator of ILC1 function.

Purpose of the Study:

• To investigate the precise role and tissue-specific expression of Hobit in ILC1s and natural killer (NK) cells.
• To determine the impact of Zfp683 deletion on ILC1 and NK cell populations and functions.

Main Methods:

• Utilized Zfp683 reporter mice to track Hobit expression.
• Analyzed Hobit expression patterns in various tissues (liver, intestinal mucosa, salivary glands) and during viral infection.
• Assessed the effects of Zfp683 deletion on ILC1 and NK cell populations and effector functions (cytokine and granzyme production).

Main Results:

• Hobit expression correlates with ILC1s in a tissue- and context-dependent manner.
• In liver and intestinal mucosa, Zfp683 expression aligns with ILC1s; in salivary glands, it defines a unique ILC1-like NK cell population.
• Zfp683 deletion impacted ILC1 numbers and function differently across tissues, affecting granzyme and IFNγ production, but did not impair NK cell-mediated viral control.

Conclusions:

• Hobit plays a dual role in ILC1 biology: maintaining ILC1 numbers in the liver and promoting functional maturation in other tissues.
• Hobit influences ILC1-like NK cells by controlling TCF1, Eomes, and granzyme expression, highlighting its complex regulatory functions in innate lymphoid cells.