• Dividing walls: How immune cells enter t

    From ScienceDaily@1:317/3 to All on Thu Apr 21 22:30:50 2022
    Dividing walls: How immune cells enter tissue

    Date:
    April 21, 2022
    Source:
    Institute of Science and Technology Austria
    Summary:
    To get to the places where they are needed, immune cells not
    only squeeze through tiny pores. They even overcome wall-like
    barriers of tightly packed cells. Scientists have now discovered
    that cell division is key to their success. Together with other
    recent studies, their findings give the full picture of a process
    just as important for healing as for the spread of cancer.



    FULL STORY ==========================================================================
    To get to the places where they are needed, immune cells not only squeeze through tiny pores. They even overcome wall-like barriers of tightly
    packed cells. Scientists at the Institute of Science and Technology
    Austria (ISTA) have now discovered that cell division is key to their
    success. Together with other recent studies, their findings published
    in Science magazine give the full picture of a process just as important
    for healing as for the spread of cancer.


    ========================================================================== Imagine a stone wall in the countryside. Tightly packed, one stone sits
    on top of the other filling the tiniest gaps. A seemingly unbreachable obstacle. On their way throughout the body to fight infections, immune
    cells face such barriers in the form of cell-dense tissues. To do their
    job as the body's rescue service, they need to find a way through. In
    a recent study, scientists from ISTA's Siekhaus group together with collaborators from the European Molecular Biology Laboratory (EMBL)
    and three students from a local High School, took a close look at how
    this happens in fruit fly embryos.

    During the development of these tiny, transparent animals, macrophages,
    the dominant form of immune cells in fruit flies, infiltrate
    tissues. Using high- end microscopes, the scientists were able to follow
    their journey. "The macrophages arrive at the wall and look for the right
    place to enter," explains Maria Akhmanova, until recently a postdoc at
    Daria Siekhaus' research group and first author of the study.

    Breaking new ground Cues that guide the macrophages have directed them to
    the right spot. There, the pioneer macrophage, the first cell to move in,
    is waiting. Suddenly, a part of the wall starts to move. The cell right in front of the macrophage rounds up, preparing to divide -- a normal part
    of its cell cycle. "This is what the pioneer has been waiting for," says Akhmanova. Moving its cell nucleus ahead, the pioneer cell now pushes
    forward while all the other macrophages follow in its tracks. As the
    Siekhaus group also recently discovered, to break through the pioneer
    gets an extra boost of energy through a complex process governed by a
    newly discovered protein the scientists named Atossa. Furthermore, the scientists learned that to shield their sensitive nucleus from damage,
    the macrophages develop protective armor made from actin filaments.

    Cell division crucial for success By precisely inhibiting, slowing down,
    and speeding up the division specifically of the flanking tissue cells,
    the researchers were now able to prove that the crucial component that
    allows immune cells to enter is in fact surrounding cell division. As
    it rounds up to prepare for division, the tissue cell at the entry site
    loses some of its connection points to its surroundings, the researchers observed through live imaging. In collaboration with the De Renzis lab
    at EMBL, the researchers also artificially induced rounding through a
    cutting edge technique using light to induce genetic changes. This wasn't sufficient to get the macrophages to enter. But genetically reducing the
    amount of the cell connections was. "It was very exciting to see how the macrophages were only able to enter the tissue when the tissue cell lost
    its connections," says Akhmanova.

    Powerful implications for cancer research "Cell division being the
    key process that controls macrophage infiltration is really a very
    elegant concept with powerful implications," Professor Daria Siekhaus
    enthuses. The same mechanism that helps macrophages enter tissues could
    also be essential for many other types of immune cells in vertebrates like humans. In the long run, the scientists are eager to learn if manipulating
    the connections or the divisions of the tissue cells could help increase
    immune cells' infiltration of tumors to fight them from within or help
    reduce immune cells' ability to attack tissues during autoimmunity. "Our findings will also affect any researcher who is working on any migrating
    cell in the context of the body," the cell biologist explains.

    For her study, the theoretical biophysicist and Lise Meitner fellow
    Maria Akhmanova delved deep into the world of microscopy. With the help
    of her mentor Daria Siekhaus, she learned everything she could about
    the fascinating and very helpful fruit flies. Three students from the Klosterneuburg High School were also part of the team. During a school
    trip to the Institute's laboratories, they discovered their enthusiasm
    for research. Consequently they helped Akhmanova with crossing and
    identifying fruit flies and even wrote an algorithm to speed up image
    analysis. "The success of this research project was made possible by
    joint forces from many scientists and enormous help from three motivated
    high school students!" says Akhmanova.

    The ISTA project part was supported by funding from the Austrian Science
    Fund FWF: Lise Meitner Fellowship.

    Video: https://youtu.be/IdVBkLXYfXg

    ========================================================================== Story Source: Materials provided by Institute_of_Science_and_Technology_Austria. Note: Content may be edited
    for style and length.


    ========================================================================== Journal Reference:
    1. Maria Akhmanova, Shamsi Emtenani, Daniel Krueger, Attila Gyoergy,
    Mariana
    Guarda, Mikhail Vlasov, Fedor Vlasov, Andrei Akopian, Aparna
    Ratheesh, Stefano De Renzis, Daria E. Siekhaus. Cell division
    in tissues enables macrophage infiltration. Science, 2022; 376
    (6591): 394 DOI: 10.1126/ science.abj0425 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220421141530.htm

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