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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Molecular Innate Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1426869

PTX3 IS EXPRESSED IN TERMINAL LYMPHATICS AND SHAPES THEIR ORGANIZATION AND FUNCTION

Provisionally accepted
Alberto Mantovani Alberto Mantovani 1*Andrea Doni Andrea Doni 1*Marina Sironi Marina Sironi 1ANNALISA DEL PRETE ANNALISA DEL PRETE 2Fabio Pasqualini Fabio Pasqualini 1Sonia Valentino Sonia Valentino 1Ivan Cuccovillo Ivan Cuccovillo 3Michela Calvi Michela Calvi 1Antonella Tosoni Antonella Tosoni 4Gianluca Vago Gianluca Vago 4Manuela Nebuloni Manuela Nebuloni 4Cecilia Garlanda Cecilia Garlanda 1Annunciata Vecchi Annunciata Vecchi 1Barbara Bottazzi Barbara Bottazzi 1*
  • 1 Humanitas Research Hospital, Rozzano, Italy
  • 2 University of Brescia, Brescia, Lombardy, Italy
  • 3 San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Milan, Lombardy, Italy
  • 4 University of Milan, Milan, Lombardy, Italy

The final, formatted version of the article will be published soon.

    The lymphatic system is a multifaceted regulator of tissue homeostasis and an integral part of immune responses. Previous studies had shown that subsets of lymphatic endothelial cells (LEC) express PTX3, an essential component of humoral innate immunity and tissue homeostasis. In the present study we found that PTX3 is localized in the extracellular matrix (ECM) surrounding human and murine lymphatic vessels (LV). In murine tissues, PTX3 was localized in the ECM close to LV terminals and sprouting. Ptx3-deficient mice showed LV abnormalities in the colon submucosa and diaphragm, including a disorganized pattern and hyperplasia of initial LV capillaries associated with altered distribution of tight junction-associated molecules. Mice with LEC-restricted PTX3 gene inactivation showed morphological and organization abnormalities similar to those observed in Ptx3-deficient animals. Ptx3-deficient mice showed defective fluid drainage from footpads and defective dendritic cell (DC) trafficking. Thus, PTX3 is strategically localized in the ECM of specialized LV, playing an essential role in their structural organization and immunological function.

    Keywords: innate immunity, Pattern recognition molecule, Extracellular Matrix, tissue homeostasis, Lymphatic System

    Received: 02 May 2024; Accepted: 23 Oct 2024.

    Copyright: © 2024 Mantovani, Doni, Sironi, DEL PRETE, Pasqualini, Valentino, Cuccovillo, Calvi, Tosoni, Vago, Nebuloni, Garlanda, Vecchi and Bottazzi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Alberto Mantovani, Humanitas Research Hospital, Rozzano, 20089, Italy
    Andrea Doni, Humanitas Research Hospital, Rozzano, 20089, Italy
    Barbara Bottazzi, Humanitas Research Hospital, Rozzano, 20089, Italy

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