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The mRNA methyltransferase Mettl3 modulates cytokine mRNA stability and limits functional responses in mast cells

Cristina Leoni1, Marian Bataclan2, Taku Ito-Kureha3

  • 1Institute for Research in Biomedicine, Università della Svizzera italiana (USI), 6500, Bellinzona, Switzerland. cristina.leoni@irb.usi.ch.

Nature Communications
|June 29, 2023
PubMed

Insights

The N6-methyladenosine (m6A) RNA modification machinery is crucial for mast cell growth and controlling inflammation. Depleting Mettl3 in mast cells worsens allergic responses by increasing inflammatory cytokines like IL-13.

Area of Science:

  • Immunology
  • Molecular Biology
  • RNA Biology

Background:

  • Mast cells are key players in allergic diseases like asthma and anaphylaxis.
  • The RNA modification N6-methyladenosine (m6A) influences immune cell function, but its role in mast cells is unknown.

Purpose of the Study:

  • To investigate the role of the m6A mRNA methyltransferase complex in mast cell function.
  • To explore how m6A modification impacts mast cell proliferation, survival, and effector responses.

Main Methods:

  • Genetic manipulation of primary mast cells.
  • In vitro and in vivo studies assessing mast cell effector functions.
  • Analysis of inflammatory cytokine expression and mRNA stability, focusing on IL-13.

Main Results:

  • The m6A methyltransferase complex regulates mast cell proliferation and survival.
  • Depletion of Mettl3 enhances mast cell effector functions and inflammatory cytokine production.
  • Mettl3 regulates IL-13 mRNA stability in an enzymatic activity-dependent manner.

Conclusions:

  • The m6A machinery is essential for maintaining mast cell homeostasis.
  • m6A modification in mast cells restrains inflammatory responses and supports cell growth.

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