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Inflammatory comorbidities: to train or not to train?

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Inflammatory stimuli train hematopoietic stem cells (HSCs) to produce more inflammatory myeloid cells. This finding links inflammation and comorbidities by showing how HSC training impacts immune responses.

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Area of Science:

  • Immunology
  • Hematology
  • Cellular Biology

Background:

  • Innate immune cells can be reprogrammed by inflammatory stimuli to mount enhanced responses to subsequent challenges, a phenomenon known as trained immunity.
  • Trained immunity involves epigenetic and metabolic changes in immune cells, leading to a more robust response upon re-exposure to stimuli.

Purpose of the Study:

  • To investigate whether hematopoietic stem cells (HSCs) can be trained by inflammatory stimuli.
  • To elucidate the mechanism by which trained HSCs influence myeloid cell production and inflammatory responses.

Main Methods:

  • The study involved exposing hematopoietic stem cells (HSCs) to inflammatory stimuli in vitro and in vivo.
  • Analysis of myeloid progeny generated from trained HSCs, including their inflammatory potential.
  • Assessment of gene expression and epigenetic modifications in trained HSCs and their progeny.

Main Results:

  • Inflammatory stimuli successfully trained hematopoietic stem cells (HSCs).
  • Trained HSCs produced myeloid progeny with an enhanced inflammatory profile.
  • This reprogramming of HSCs mechanistically links inflammatory stimuli to the generation of inflammatory comorbidities.

Conclusions:

  • Hematopoietic stem cells (HSCs) possess the capacity for trained immunity.
  • Training of HSCs provides a cellular mechanism connecting inflammatory stimuli to the development of inflammatory comorbidities.
  • Targeting HSC training may offer novel therapeutic strategies for inflammatory diseases.