A Theoretical Hypothesis on How Immune Cells May Transmit Acquired Traits: A Macrophage-piRNA Pathway for...

Area of Science:

• Epigenetics and developmental biology
• RNA biology
• Evolutionary biology

Background:

• Environmental exposures can induce heritable phenotypic changes across generations.
• The cellular mechanisms connecting somatic stress to germline transmission are not well understood.
• Small non-coding RNAs, including PIWI-interacting RNAs (piRNAs), are implicated in epigenetic inheritance.

Purpose of the Study:

• To review the evidence linking piRNAs, macrophage biology, and environmentally induced transgenerational inheritance.
• To propose a novel model for how environmental stress can lead to heritable morphological variation.

Main Methods:

• Literature review of studies on small RNA inheritance in various organisms (animals, plants, ciliates).
• Examination of research on macrophage polarization and extracellular vesicle communication.
• Revisiting the Drosophila ELBO phenotype as a case study.

Main Results:

• piRNAs are key players in epigenetic inheritance, involved in transposable element silencing and chromatin regulation.
• Macrophage polarization states exhibit distinct piRNA signatures and release extracellular vesicles containing non-coding RNAs.
• The macrophage-mediated morphological evolution (M3) model is proposed to link environmental stress to transgenerational phenotypes.

Conclusions:

• piRNAs and macrophage signaling represent plausible cellular routes for transmitting environmentally induced epigenetic information across generations.
• The M3 model provides a testable framework for understanding how environmental stress can drive heritable morphological evolution.