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      Structural and functional changes to lymph nodes in ageing mice

      research-article
      1 , 1 ,
      Immunology
      John Wiley and Sons Inc.
      ageing, follicular dendritic cells, lymph node, macrophages, stromal cells

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          Summary

          Lymph nodes ( LN) are secondary lymphoid organs spread throughout the lymphatic system. They function to filter pathogenic material from the lymphatic fluid to maintain the health of the organism. Subcapsular sinus macrophages ( SCSM) are among the first‐responders within the LN due to their strategic location within the subcapsular sinus region. These macrophages aid the delivery of immune complexes to B cells and follicular dendritic cells ( FDC) within the LN. Here we show an increase in SCSM and other macrophage populations within aged LN. However, immune complex uptake by macrophages within LN was not altered with age, nor was immune complex uptake by B cells. LN stromal cell populations, important in immune responses and the localization and survival of leucocytes, were altered in their representation and distribution in aged LN. In particular, FDC regions were decreased in size and had decreased chemokine CXCL13 expression. Furthermore, the retention of immune complexes by FDC was decreased in aged LN at 24 hr post‐injection. As FDC are important in the maintenance of germinal centre responses, the decreased retention of immune complex in aged LN may contribute to the reduced germinal centre responses observed in aged mice.

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          Most cited references28

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          Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells.

          Interleukin 7 is essential for the survival of naive T lymphocytes. Despite its importance, its cellular source in the periphery remains poorly defined. Here we report a critical function for lymph node access in T cell homeostasis and identify T zone fibroblastic reticular cells in these organs as the main source of interleukin 7. In vitro, T zone fibroblastic reticular cells were able to prevent the death of naive T lymphocytes but not of B lymphocytes by secreting interleukin 7 and the CCR7 ligand CCL19. Using gene-targeted mice, we demonstrate a nonredundant function for CCL19 in T cell homeostasis. Our data suggest that lymph nodes and T zone fibroblastic reticular cells have a key function in naive CD4(+) and CD8(+) T cell homeostasis by providing a limited reservoir of survival factors.
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            Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes.

            After entry into lymph nodes (LNs), B cells migrate to follicles, whereas T cells remain in the paracortex, with each lymphocyte type showing apparently random migration within these distinct areas. Other than chemokines, the factors contributing to this spatial segregation and to the observed patterns of lymphocyte movement are poorly characterized. By combining confocal, electron, and intravital microscopy, we showed that the fibroblastic reticular cell network regulated naive T cell access to the paracortex and also supported and defined the limits of T cell movement within this domain, whereas a distinct follicular dendritic cell network similarly served as the substratum for movement of follicular B cells. These results highlight the central role of stromal microanatomy in orchestrating cell migration within the LN.
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              Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks

              Lymph node stromal cells (LNSCs) closely regulate immunity and self-tolerance, yet key aspects of their biology remain poorly illuminated. Comparative transcriptomic analyses of murine LNSC subsets revealed expression of important immune mediators, growth factors, and novel structural components. Pairwise analyses of ligands and cognate receptors across hematopoietic and stromal subsets suggested a complex web of cross-talk. Compared with skin and thymic fibroblasts, fibroblastic reticular cells (FRCs) were enriched in genes relevant to cytokine signaling. LNSCs from inflamed lymph nodes upregulated acute phase response genes, chemokines, and antigen presentation genes. Poorly studied podoplanin−CD31− LNSCs showed similarities to FRCs, but lacked IL-7 expression, and were identified as myofibroblastic integrin α7+ pericytes. Together these data comprehensively describe the transcriptional characteristics of LNSC subsets.
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                Author and article information

                Contributors
                neil.mabbott@roslin.ed.ac.uk
                Journal
                Immunology
                Immunology
                10.1111/(ISSN)1365-2567
                IMM
                Immunology
                John Wiley and Sons Inc. (Hoboken )
                0019-2805
                1365-2567
                16 March 2017
                June 2017
                16 March 2017
                : 151
                : 2 ( doiID: 10.1111/imm.2017.151.issue-2 )
                : 239-247
                Affiliations
                [ 1 ] The Roslin Institute and Royal (Dick) School of Veterinary SciencesUniversity of Edinburgh MidlothianUK
                Author notes
                [*] [* ] Correspondence: Neil A. Mabbott, The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK. Email: neil.mabbott@ 123456roslin.ed.ac.uk

                Senior author: Neil A. Mabbott

                Author information
                http://orcid.org/0000-0002-2013-2559
                http://orcid.org/0000-0001-7395-1796
                Article
                IMM12727
                10.1111/imm.12727
                5418465
                28207940
                e071ca9f-0bd0-445e-a9a4-6b1f7edd1eef
                © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 January 2017
                : 09 February 2017
                : 09 February 2017
                Page count
                Figures: 5, Tables: 0, Pages: 9, Words: 5410
                Funding
                Funded by: Biotechnological and Biological Sciences Research Council
                Award ID: BB/L007452/1
                Award ID: BB/J004227/1
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                imm12727
                June 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.9 mode:remove_FC converted:05.05.2017

                Immunology
                ageing,follicular dendritic cells,lymph node,macrophages,stromal cells
                Immunology
                ageing, follicular dendritic cells, lymph node, macrophages, stromal cells

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