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Review
. 2023 Nov:70:101817.
doi: 10.1016/j.smim.2023.101817. Epub 2023 Aug 10.

Aging of lymphoid stromal architecture impacts immune responses

Jessica N Lancaster  1
Affiliations
Review

Aging of lymphoid stromal architecture impacts immune responses

Jessica N Lancaster. Semin Immunol. 2023 Nov.

Abstract

The secondary lymphoid organs (SLOs) undergo structural changes with age, which correlates with diminishing immune responses against infectious disease. A growing body of research suggests that the aged tissue microenvironment can contribute to decreased immune function, independent of intrinsic changes to hematopoietic cells with age. Stromal cells impart structural integrity, facilitate fluid transport, and provide chemokine and cytokine signals that are essential for immune homeostasis. Mechanisms that drive SLO development have been described, but their roles in SLO maintenance with advanced age are unknown. Disorganization of the fibroblasts of the T cell and B cell zones may reduce the maintenance of naïve lymphocytes and delay immune activation. Reduced lymphatic transport efficiency with age can also delay the onset of the adaptive immune response. This review focuses on recent studies that describe age-associated changes to the stroma of the lymph nodes and spleen. We also review recent investigations into stromal cell biology, which include high-dimensional analysis of the stromal cell transcriptome and viscoelastic testing of lymph node mechanical properties, as they constitute an important framework for understanding aging of the lymphoid tissues.

Keywords: Aging; Endothelium; Fibroblast; Lymphatics; Stroma; Tissue microenvironment.

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Figures

Figure 1.
Figure 1.. Age-associated changes to lymph node architecture.
The lymph node is organized into compartments that express CCL19 and CCL21 (orange) in the T cell zone or CXCL13 (purple) in the B cell follicles. In adulthood (young- left panel), CCL19/21 and CXCL13 expression organizes the T cell and B cell zones. With advanced age (aged- right panel) the lymph node is atrophied, and chemokine expression is reduced and less responsive to immune activation. Contraction of lymphatic vessels deliver solutes and cells via the lymph, but lymphatic vessels with age become more permeable and generate less contractile force. Within the cellular niches of the T cell zone, B cell follicle, and subcapsular sinus (insets) specialized stroma create structures to coordinate hematopoietic cell function. The aged T cell zone is smaller, with increased fibrosis and/or lipomatosis. The aged B cell follicle loses its definition and harbors less follicular dendritic cells (FDCs) during the germinal center response. Lymphatics drain into the subcapsular sinus to allow antigen sampling from the lymph. With age, collagen of the capsule is thickened, gaps between stromal cells widen, though macrophage numbers remain constant. Stroma elements and hematopoietic cells are color-coded in the top right legend.
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