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Immunofluorescent characterization of innervation and nerve-immune cell neighborhood in mouse thymus

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Abstract

The central nervous system impacts the immune system mainly by regulating the systemic concentration of humoral substances, whereas the peripheral nervous system (PNS) communicates with the immune system specifically according to local “hardwiring” of sympathetic/parasympathetic (efferent) and sensory (afferent) nerves to the primary and secondary lymphoid tissue/organs (e.g., thymus spleen and lymph nodes). In the present study, we use immunofluorescent staining of neurofilament-heavy to reveal the distribution of nerve fibers and the nerve-immune cell neighborhood inside the mouse thymus. Our results demonstrate (a) the presence of an extensive meshwork of nerve fibers in all thymic compartments, including the capsule, subcapsular region, cortex, cortico-medullary junction and medulla; (b) close associations of nerve fibers with blood vessels (including the postcapillary venules), indicating the neural control of blood circulation and immune cell dynamics inside the thymus; (c) the close proximity of nerve fibers to various subsets of thymocytes (e.g., CD4+, CD8+ and CD4+CD8+), dendritic cells (e.g., B220+, CD4+, CD8+ and F4/80+), macrophages (Mac1+ and F4/80+) and B cells. Our novel findings concerning thymic innervation and the nerve-immune cell neighborhood in situ should facilitate the understanding of bi-directional communications between the PNS and primary lymphoid organs. Since the innervation of lymphoid organs, including the thymus, may play essential roles in the pathogenesis and progression of some neuroimmune, infectious and autoimmune diseases, better knowledge of PNS-immune system crosstalk should benefit the development of potential therapies for these diseases.

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Acknowledgments

The authors thank Wayne Rasband for the ImageJ program.

Funding

H.A.M.A. is funded by a PhD scholarship (Grant no. 4394) from the Ministry of Higher Education & Scientific Research of Iraq.

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Authors and Affiliations

  1. Discipline of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA, 6150, Australia

    Huda A. M. Al-Shalan, Philip K. Nicholls, Wayne K. Greene & Bin Ma

  2. Department of Microbiology/Virology, College of Veterinary Medicine, Baghdad University, Baghdad, 10070, Iraq

    Huda A. M. Al-Shalan

  3. Clinical College, Hebei Medical University, Shijiazhuang, 050031, Hebei, China

    Dailun Hu

Authors
  1. Huda A. M. Al-Shalan
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  2. Dailun Hu
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  3. Philip K. Nicholls
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  4. Wayne K. Greene
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  5. Bin Ma
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Correspondence to Bin Ma.

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The authors declare that they have no conflicts of interest.

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All animal experiments were carried out following the Australian code for the care and use of animals for scientific purposes at Murdoch University, Perth, Australia and with local animal ethics committee approval.

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Al-Shalan, H.A.M., Hu, D., Nicholls, P.K. et al. Immunofluorescent characterization of innervation and nerve-immune cell neighborhood in mouse thymus. Cell Tissue Res 378, 239–254 (2019). https://doi.org/10.1007/s00441-019-03052-4

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  • DOI: https://doi.org/10.1007/s00441-019-03052-4

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