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The molecular mediators present within the inflammatory microenvironment are able, in certain conditions, to favor the initiation of tertiary lymphoid structure (TLS) development. TLS is organized lymphocyte clusters able to support antigen-specific immune response in non-immune organs. Importantly, chronic inflammation does not always result in TLS formation; instead, TLS has been observed to develop specifically in permissive organs, suggesting the presence of tissue-specific cues that are able to imprint the immune responses and form TLS hubs. Fibroblasts are tissue-resident cells that define the anatomy and function of a specific tissue. Fibroblast plasticity and specialization in inflammatory conditions have recently been unraveled in both immune and non-immune organs revealing a critical role for these structural cells in human physiology. Here, we describe the role of fibroblasts in the context of TLS formation and its functional maintenance in the tissue, highlighting their potential role as therapeutic disease targets in TLS-associated diseases.
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http://dx.doi.org/10.1111/imr.12987 | DOI Listing |
Nat Immunol
September 2025
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Crohn's disease pathology is modeled in TNF mice that overproduce tumor necrosis factor (TNF) to drive disease through TNF receptors. An alternative ligand for TNF receptors, soluble LTα, is produced by B cells, but has received scarce attention because LTα also partners with LTβ to generate membrane-tethered LTαβ that promotes tertiary lymphoid tissue-another feature of Crohn's disease. We hypothesized that B cell-derived LTαβ would critically affect ileitis in TNF mice.
View Article and Find Full Text PDFMol Carcinog
September 2025
Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
B cells located in tertiary lymphoid structures (TLSs) may undergo clonal expansion, somatic hypermutation, isotype switching, and tumor-specific antibody production, suggesting that antibody-producing plasma cells may be involved in antitumor immunity. This study used a combination of single-cell sequencing (five samples from our center, and four samples from PRJNA662018) and spatial transcriptome (one sample from our center, and four samples from GSE169379) research methods to investigate the relationship between TLSs and the immunoglobulin repertoire in muscle invasive bladder cancer (MIBC). 405 patients with MIBC from TCGA and 348 patients with metastatic urothelial carcinoma on PD-L1 inhibitor treatment from the IMvigor210 trial were included in this study.
View Article and Find Full Text PDFFront Immunol
September 2025
Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Background: Tertiary lymphoid structures (TLSs) are linked to prognosis in esophageal squamous cell carcinoma (ESCC), but whether the distribution, abundance, and maturity of TLSs affect therapeutic efficacy and prognosis in ESCC treated with neoadjuvant chemoradiotherapy plus immunotherapy (NRCI) remains unclear. We explored TLS characteristics and correlated them with patient survival.
Methods: A total of 157 resectable ESCC patients treated with neoadjuvant therapy between September 2020 and May 2023 were divided into NRCI (n=49) and neoadjuvant chemoimmunotherapy (NCI, n=108) groups.
Immunol Rev
September 2025
Laboratory of Barrier Immunity, Division of Molecular Hematology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Lund, Sweden.
The skin is the outermost organ that serves as the host's live, microbiota-inhabited physical border, evolved to cope with continuous confrontation by a wide variety of environmental elements. This dynamic borderline is prone to injury and damage. Therefore, to deliver on the critical demands for protection, skin is tightly associated with innate and adaptive defense mechanisms that ensure homeostatic tissue barrier integrity.
View Article and Find Full Text PDFJ Immunol
September 2025
Research and Medical Affairs, Amgen Inc, Thousand Oaks, CA, United States.
The Feline McDonough sarcoma-like tyrosine kinase 3 (FLT3)/FLT3 ligand (FLT3L) pathway is associated with pathogenesis of several autoimmune diseases, including Sjögren's. Inflammatory signals increase FLT3L levels; FLT3L signaling promotes further inflammation through the differentiation, function, and survival of immune cells, including dendritic cells (DCs), monocytes, and B cells. Patients with Sjögren's have elevated FLT3L levels, increased infiltration of DCs, macrophages, and B cells into salivary glands and tertiary lymphoid structures (TLS).
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