Editorial - Exploring immune-stromal cell dynamics - pathways and therapeutic implications

Sep 28, 2026

Editorial exploring immune-stromal cell dynamics and their bidirectional roles in immune homeostasis and disease pathogenesis. Stromal cells are presented as integral immune components that shape tissue homeostasis, inflammatory responses, and disease progression across multiple systems. Advances in omics, including single-cell and spatial transcriptomics, reveal stromal molecular phenotypes and their function as immune sentinels, while receptor-ligand bioinformatic tools clarify dysregulated immune–stromal crosstalk. The article highlights stromal subsets as therapeutic targets and modalities, summarizing reviews and studies on lymphoid architecture, germinal center regulation, ECM remodeling, and AAA and EMT-driven remodeling in asthma.

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Editorial on the Research Topic

Exploring immune-stromal cell dynamics: pathways and therapeutic implications

Stromal cells as immune components and sentinels

Omics advances and receptor-ligand crosstalk tools

Stromal subsets in secondary lymphoid organs

Fibroblasts, FDCs, and germinal center orchestration

Disease microenvironments from immune-stromal interactions

TYPE Editorial PUBLISHED 15 December 2025 DOI 10.3389/fimmu.2025.1744273 OPEN ACCESS EDITED AND REVIEWED BY Raphaela Goldbach-Mansky, National Institute of Allergy and Infectious Diseases (NIH), United States *CORRESPONDENCE Stephen B Gauld [stephen.gauld@abbvie.com](stephen.gauld@abbvie.com) RECEIVED 11 November 2025 ACCEPTED 27 November 2025 PUBLISHED 15 December 2025 CORRECTED 19 December 2025 CITATION Ryu S, Gauld SB, Staron MM, Odell ID, Cash JL and Radstake TRDJ (2025) Editorial: Exploring immune-stromal cell dynamics: pathways and therapeutic implications. Front. Immunol. 16:1744273 . doi: 10.3389/fimmu.2025.1744273 COPYRIGHT © 2025 Ryu, Gauld, Staron, Odell, Cash and Radstake. 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) and the copyright owner(s) 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. Editorial: Exploring immune stromal cell dynamics: pathways and therapeutic implications Stacy Ryu 1, Stephen B Gauld 1*, Matthew M Staron 1, Ian D Odell 2, Jenna L Cash 3 and Timothy RDJ Radstake 1 1Abbvie Inc., North Chicago, IL and Cambridge, MA, United States, 2 Department of Dermatology, Yale School of Medicine, Department of Immunobiology, Yale University School of Medicine, New Haven, CT, United States, 3Centre for Inﬂammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom KEYWORDS tissue resident immune cells, ﬁbroblast and immune crosstalk, tertiary lymphoid structures, cell-cell interactions, mesenchymal stem/stromal cells Editorial on the Research Topic Exploring immune-stromal cell dynamics: pathways and therapeutic implications Bidirectional immune-stromal cell dynamics play a pivotal role in immune homeostasis and disease pathogenesis. Accumulating data demonstrates that stromal cells are more than mere structural components; rather, they constitute a key part of the immune system. Speciﬁcally, stromal cells have been shown to shape tissue homeostasis, inﬂammatory responses, and disease progression in various tissues-including pulmonary, lymphoid, and vascular systems. Advances in omics technologies (single cell and spatial transcriptomics) have uncovered the molecular phenotypes of stromal cells and illuminate their potential as key immune sentinels, capable of regulating the inﬂammatory milieu by detecting danger signals and releasing soluble mediators. Novel bioinformatic tools that enable analyses of complex receptor-ligand interactions have further uncovered how dysregulated crosstalk between immune and stromal cells can drive the initiation and progression of such disorders. Given their role as orchestrators of the immune response, stromal cell types are investigated both as therapeutic targets and as therapeutic modalities/approaches. The current Research Topic aims to deepen our understanding of the molecular proﬁles, mechanisms and pathways of stromal cells that govern immune cell regulation, while shedding light on their therapeutic potential. Yasmin et al. provided a comprehensive review on the architectural and functional diversity of stromal subsets in secondary lymphoid organs. The authors summarize key ﬁndings on the heterogeneous molecular phenotypes of distinct stromal populations such as ﬁbroblastic reticular cells (FRCs), follicular dendritic cells (FDCs), marginal reticular cells, and adventitial cells in lymph nodes, spleen, and Peyer’s patches. These subsets occupy discrete anatomical niches throughout secondary lymphoid organs and provide scaffolding critical for immune cell migration, antigen presentation, germinal center (GC) formation and orchestration of

FAQs

What role do immune-stromal cell dynamics play in disease?

They contribute bidirectionally to immune homeostasis and to immune system dysregulation that drives disease pathogenesis.

How do omics technologies inform understanding of stromal cells?

Single-cell and spatial transcriptomics reveal stromal molecular phenotypes and help identify how stromal cells regulate the inflammatory milieu.

Why are stromal cell types considered in therapeutic research?

Because they orchestrate immune responses, stromal subsets are investigated as therapeutic targets and as therapeutic modalities or approaches.

Sep 28, 2026

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