A local subset of mesenchymal cells expressing the transcription factor Osr1 orchestrates lymph node initiation

Pedro Vallecillo-García; Mickael Orgeur; Glenda Comai; Sophie Poehle-Kronawitter; Cornelius Fischer; Marleen Gloger; Camille E Dumas; Claudia Giesecke-Thiel; Sascha Sauer; Shahragim Tajbakhsh; Uta E Höpken; Sigmar Stricker

doi:10.1016/j.immuni.2023.04.014

A local subset of mesenchymal cells expressing the transcription factor Osr1 orchestrates lymph node initiation

Immunity. 2023 Jun 13;56(6):1204-1219.e8. doi: 10.1016/j.immuni.2023.04.014. Epub 2023 May 8.

Affiliations

¹ Institute for Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany. Electronic address: [email protected].
² Institut Pasteur, Université Paris Cité, CNRS UMR 6047, Unit for Integrated Mycobacterial Pathogenomics, 75015 Paris, France.
³ Institut Pasteur, Stem Cells & Development Unit, CNRS UMR 3738, Paris, France.
⁴ Institute for Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
⁵ Core Facility Genomics, Berlin Institute of Health at Charité, 10178 Berlin, Germany; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 10115, Berlin, Germany.
⁶ Max Delbrück Center for Molecular Medicine, Department of Translational Tumor Immunology, 13125 Berlin, Germany; Uppsala University, Immunology Genetics and Pathology, 75237 Uppsala, Sweden.
⁷ Aix-Marseille Université, CNRS UMR 7288, IBDM, 13009 Marseille, France.
⁸ Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
⁹ Max Delbrück Center for Molecular Medicine, Department of Microenvironmental Regulation in Autoimmunity and Cancer, 13125 Berlin, Germany.
¹⁰ Institute for Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany. Electronic address: [email protected].

PMID: 37160119
DOI: 10.1016/j.immuni.2023.04.014

Abstract

During development, lymph node (LN) initiation is coordinated by lymphoid tissue organizer (LTo) cells that attract lymphoid tissue inducer (LTi) cells at strategic positions within the embryo. The identity and function of LTo cells during the initial attraction of LTi cells remain poorly understood. Using lineage tracing, we demonstrated that a subset of Osr1-expressing cells was mesenchymal LTo progenitors. By investigating the heterogeneity of Osr1⁺ cells, we uncovered distinct mesenchymal LTo signatures at diverse anatomical locations, identifying a common progenitor of mesenchymal LTos and LN-associated adipose tissue. Osr1 was essential for LN initiation, driving the commitment of mesenchymal LTo cells independent of neural retinoic acid, and for LN-associated lymphatic vasculature assembly. The combined action of chemokines CXCL13 and CCL21 was required for LN initiation. Our results redefine the role and identity of mesenchymal organizer cells and unify current views by proposing a model of cooperative cell function in LN initiation.

Keywords: CXCL13; Osr1; initiation; lymph nodes; lymphatic vessel; mesenchymal; retinoic acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation
Lymph Nodes
Lymphoid Tissue
Organogenesis*
Transcription Factors*

Substances

Transcription Factors