4.7 Article

Ectopic lymphoid structures in the aged lacrimal glands

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CLINICAL IMMUNOLOGY
卷 248, 期 -, 页码 -

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ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2023.109251

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Aging; Ectopic lymphoid structures; Tertiary lymphoid organs; Lacrimal gland; Dry eye; B cells

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Aging is a complex biological process that affects multiple organs. In this study, the authors investigated the changes in the immune landscape of aged lacrimal glands (LGs) in mice. They found increased lymphoid infiltrates and ectopic lymphoid structures in aged LGs, as well as alterations in B and T cell populations and gene expression associated with immune activation and germinal center formation. These findings indicate a profound change in the immune response of aged LGs, with B cells becoming predominant.
Aging is a complex biological process in which many organs are pathologically affected. We previously reported that aged C57BL/6J had increased lacrimal gland (LG) lymphoid infiltrates that suggest ectopic lymphoid structures. However, these ectopic lymphoid structures have not been fully investigated. Using C57BL/6J mice of different ages, we analyzed the transcriptome of aged murine LGs and characterized the B and T cell populations. Age-related changes in the LG include increased differentially expressed genes associated with B and T cell activation, germinal center formation, and infiltration by marginal zone-like B cells. We also identified an age-related increase in B1+ cells and CD19+B220+ cells. B220+CD19+ cells were GL7+ (germinal center-like) and marginal zone-like and progressively increased with age. There was an upregulation of transcripts related to T follicular helper cells, and the number of these cells also increased as mice aged. Compared to a mouse model of Sjo center dot gren syndrome, aged LGs have similar transcriptome responses but also unique ones. And lastly, the ectopic lymphoid structures in aged LGs are not exclusive to a specific mouse background as aged diverse outbred mice also have immune infiltration. Altogether, this study identifies a profound change in the immune landscape of aged LGs where B cells become predominant. Further studies are necessary to investigate the specific function of these B cells during the aged LGs.

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