title: Premature thymic involution is independent of structural plasticity of the thymic stroma.
abstract: The thymus is the organ devoted to T-cell production. The thymus undergoes multiple rounds of atrophy and redevelopment before degenerating with age in a process known as involution. This process is poorly understood, despite the influence the phenomenon has on peripheral T-cell numbers. Here we have investigated the FVB/N mouse strain, which displays premature thymic involution. We find multiple architectural and cellular features that precede thymic involution, including disruption of the epithelial-endothelial relationship and a progressive loss of pro-T cells. The architectural features, reminiscent of the human thymus, are intrinsic to the nonhematopoietic compartment and are neither necessary nor sufficient for thymic involution. By contrast, the loss of pro-T cells is intrinsic to the hematopoietic compartment, and is sufficient to drive premature involution. These results identify pro-T-cell loss as the main driver of premature thymic involution, and highlight the plasticity of the thymic stroma, capable of maintaining function across diverse interstrain architectures.
authors: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium.|Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors: Dean
authors: D
authors: Franckaert
authors: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium.|Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors: Susan M
authors: SM
authors: Schlenner
authors: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium.|Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors: Nathalie
authors: N
authors: Heirman
authors: Mechanisms of Cancer, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors: Jason
authors: J
authors: Gill
authors: Department of Rheumatology and Inflammation Research, Göteborg University, Gothenburg, Sweden.
authors: Gabriel
authors: G
authors: Skogberg
authors: Department of Rheumatology and Inflammation Research, Göteborg University, Gothenburg, Sweden.
authors: Olov
authors: O
authors: Ekwall
authors: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium.|Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors: Karen
authors: K
authors: Put
authors: Lymphocyte Signaling and Development ISP, Babraham Institute, Cambridge, UK.
authors: Michelle A
authors: MA
authors: Linterman
authors: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium.|Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors: James
authors: J
authors: Dooley
authors: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium.
authors: Adrian
authors: A
authors: Liston
mesh_terms: D000375:Aging / Q000276:immunology / Q000473:pathology; D000818:Animals; D001284:Atrophy / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D004730:Endothelium, Vascular / Q000473:pathology; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013045:Species Specificity; D017154:Stromal Cells / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000098:blood supply / Q000276:immunology* / Q000473:pathology*
keywords: FVB/N mouse; Involution; Pro-T cells; Thymic epithelium cells; Thymus; Vascularization
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