tRNA m1A modification is essential for gut homeostasis and function of group 3 innate lymphoid cells

TL;DR

This study shows that a specific tRNA modification is essential for gut health and the function of immune cells called ILC3s.

Contribution

The study reveals a new role for TRMT61A-mediated m1A tRNA modification in regulating ILC3s and gut immunity.

Findings

TRMT61A is predominantly expressed in ILC3s and its depletion disrupts cell cycle and reduces cell numbers.

Mice lacking TRMT61A in ILC3s show gut dysbiosis and increased susceptibility to intestinal inflammation and infection.

Antibiotic treatment can restore ILC3 levels in TRMT61A-deficient mice.

Abstract

Group 3 innate lymphoid cells (ILC3s) play crucial roles in maintaining intestinal homeostasis and defending against bacterial infections. However, the epigenetic mechanisms that regulate ILC3 responses are not well understood. In this study, we show that Trmt61a, the methyltransferase responsible for the m1A58 tRNA modification, is predominantly expressed in ILC3s. We found that specific depletion of TRMT61A in ILC3s leads to dysregulated cell cycle and a reduction in cell numbers. Notably, mice with an ILC3-specific TRMT61A deficiency exhibit dysbiosis, but antibiotic treatment can restore colonic ILC3 levels. Furthermore, these mice exhibit increased susceptibility to experimental intestinal inflammation and enteric bacterial infection. Our findings uncover a previously unrecognized role for TRMT61A mediated m1A modification in the regulation of intestinal ILC3s, essential for protecting intestinal tissue during inflammation and enhancing innate immunity against enteric pathogens.

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