What is it about?
Lymph node extracellular matrix (ECM) proteoglycans, produced by non-immune stromal cells such as fibroblastic reticular cells (FRCs), play an active role in regulating adaptive immunity. Beyond providing structural support, these ECM components influence the proliferation, activation, and differentiation of T lymphocytes. In particular, certain ECM proteoglycans like lumican, biglycan and decorin, modulate Th1 cell responses through paracrine signaling mechanisms, shaping the local cytokine milieu and potentially interacting with T cell surface receptors. This reveals a novel immunoregulatory function of the lymph node stromal matrix, highlighting how the ECM can directly influence the quality and magnitude of T cell-mediated immunity. These findings suggest that stromal-derived ECM components are not passive scaffolds but are integral modulators of immune cell function within the lymphoid tissue microenvironment.
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Photo by National Institute of Allergy and Infectious Diseases on Unsplash
Why is it important?
One key aspect of this regulation is the paracrine modulation of T helper 1 (Th1) cells by stromal-derived proteoglycans. These ECM proteoglycans can alter the local cytokine landscape, influence antigen presentation dynamics, or engage immune cell receptors such as integrins to shape T cell fate decisions. This introduces a novel mechanism by which the ECM—not just professional antigen-presenting cells or cytokines—can directly tune the quality and magnitude of T cell responses. The implications of this are significant. It expands the functional scope of lymph node stromal cells beyond passive structural support, positioning them as integral players in immune homeostasis and response. This matrix-based regulation provides spatial context to immunity, explaining how local tissue architecture can influence immune cell behavior. Furthermore, dysregulation of ECM proteoglycan expression or function could contribute to chronic inflammation, autoimmunity, or immune evasion in cancer.
Perspectives
From a translational perspective, targeting ECM-mediated signaling pathways could offer new therapeutic avenues. Modulating ECM composition or blocking specific ECM–immune cell interactions may enhance vaccine responses, suppress autoimmunity, or improve immunotherapy outcomes. In sum, the discovery that lymph node ECM proteoglycans can directly regulate T cells underscores the importance of the stromal microenvironment in shaping adaptive immunity and opens new directions for both basic and applied immunological research.
Dr George Maiti
NYU Langone Medical Center
Read the Original
This page is a summary of: Paracrine regulations of IFN-γ secreting CD4+ T cells by lumican and biglycan are protective in allergic contact dermatitis, Matrix Biology, September 2025, Elsevier,
DOI: 10.1016/j.matbio.2025.06.002.
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