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Butyrate limits human natural killer cell effector function.

Vanessa Zaiatz-Bittencourt1, Fiona Jones2, Miriam Tosetto2

  • 1Centre for Colorectal Disease, St. Vincent's University Hospital and School of Medicine, University College Dublin, Dublin 4, Ireland. zaiatzbv@tcd.ie.

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Summary
This summary is machine-generated.

Butyrate, a microbial short-chain fatty acid (SCFA), reduces inflammation by suppressing human NK cell effector functions. This study reveals butyrate

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Area of Science:

  • Immunology
  • Microbiome Research
  • Cellular Metabolism

Background:

  • The gut microbiota influences chronic inflammation and diseases like autoimmunity and cancer.
  • Microbial metabolites, such as short-chain fatty acids (SCFAs), play a crucial role in host-microbiome interactions.
  • Butyrate, an SCFA, exhibits immunomodulatory effects, but its impact on human NK cells requires further investigation.

Purpose of the Study:

  • To investigate the effect of butyrate on the effector functions of human NK cells.
  • To elucidate the mechanisms underlying butyrate's immunomodulatory activity on NK cells.

Main Methods:

  • Human peripheral blood NK cells were stimulated with IL-12/IL-15.
  • Cells were cultured with or without butyrate.
  • NK cell activation, receptor expression, cytokine production, and metabolic activity were analyzed.
  • Shotgun proteomics was employed to identify downstream mediators.

Main Results:

  • Butyrate demonstrated a significant anti-inflammatory effect on NK cells.
  • Butyrate downregulated activating receptors (TRAIL, NKp30, NKp44) and cytokine production (IFNγ, TNF-α, IL-22, granzyme B, granzyme A, perforin).
  • Butyrate suppressed NK cell function by inhibiting mTORC1 activity, c-Myc expression, and metabolism, with BRD2, MAT2A, and EHD1 identified as mediators.

Conclusions:

  • Butyrate effectively limits human NK cell effector functions and exhibits anti-inflammatory properties.
  • The findings highlight butyrate's role in modulating NK cell-mediated immune responses.
  • This research may inform strategies to control NK cell activity in chronic inflammatory conditions.