3 high school students, together with scientists, published Science: They uncovered the key mechanism of the immune response

iNature Cells migrate through crowded microenvironments within tissues during normal development, immune responses and cancer metastasis
.

Usually, migrating cells find the path of least resistance
.

Although migration through pores and tracks in the extracellular matrix (ECM) has been well studied, little is known about cell crossing into restrictive cell-dense tissues
.

On April 21, 2022, Maria Akhmanova et al.
of the Austrian Institute of Science and Technology published a research paper entitled "Cell division in tissues enables macrophage infiltration" in Science Online, which found that Drosophila macrophages need to be in the entry site to invade embryonic tissues.
Dividing epithelial ectoderm cells
.

Dividing ectodermal cells break down ECM attachments formed by integrin-mediated mesodermal cell focal adhesions, allowing macrophages to move their nuclei forward and invade between two immediately adjacent tissues
.

Invasion efficiency depends on division frequency, but a reduction in adhesion strength allows macrophage entry independent of division
.

This work demonstrates that tissue dynamics can regulate cellular infiltration
.

It is worth mentioning that three of the authors of this paper are local high school students (Mikhail Vlasov, Fedor Vlasov and Andrei Akopian respectively), who also contributed to this research
.

The spread of cells into tissues is fundamental to the formation and maintenance of complex organisms
.

During vertebrate development, neural crest cells enter tissues to form different tissue types; immune cells enter organs to regulate tissue function and fight infection; and cancer cells enter other organs during metastasis
.

These diverse embryonic and adult environments contain tightly packed cells that adhere to each other on the extracellular matrix (ECM) between them
.

Despite its importance, little is known about the invasion of this cell-dense tissue
.

Macrophages are scavenger cells that invade tissues early in development to establish resident and patrolling organs
.

In early Drosophila embryos, macrophages follow guiding cues and invade the germinal zone (GB) at the entry point (EP) at the acute angle between the basal side of the ectoderm and the surface of the mesoderm
.

They progress further between the ectoderm and mesoderm, which are juxtaposed on a thin layer of ECM
.

During this invasion, the macrophages moved like a chain, keeping the two tissues established by the pioneers separate
.

Macrophage invasion is associated with ectodermal cell division at the point of entry (figure from Science).
The first macrophages take about 20 minutes to enter through the tissue barrier, using αPS2- and βPS-integrins bound to laminin
.

Proteolytic ECM degradation of matrix metals does not affect the efficiency of entry, but macrophage-specific programs do
.

How the dynamics and properties of surrounding cells influence macrophage tissue invasion remains unclear
.

The study found that Drosophila macrophage invasion of embryonic tissue requires division of epithelial ectoderm cells at the entry site
.

Dividing ectodermal cells break down ECM attachments formed by integrin-mediated mesodermal cell focal adhesions, allowing macrophages to move their nuclei forward and invade between two immediately adjacent tissues
.

Invasion efficiency depends on division frequency, but a reduction in adhesion strength allows macrophage entry independent of division
.

This work demonstrates that tissue dynamics can regulate cellular infiltration
.

It is worth mentioning that three of the authors of this paper are local high school students (Mikhail Vlasov, Fedor Vlasov and Andrei Akopian respectively), who also contributed to this research
.

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