1. Loss of direct adrenergic innervation after peripheral nerve injury causes lymph node expansion through IFN-γ
- Author
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Barbara U. Schraml, Christoph Scheiermann, Coline Barnoud, Elisabeth Deindl, Sophia Martina Hergenhan, Johanna Salvermoser, Manuel Lasch, Stephan Holtkamp, Alba de Juan, Burak Kizil, Louise Ince, Jasmin Weber, Chien-Sin Chen, Chen Wang, Lydia Lutes, and Dirk Baumjohann
- Subjects
Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Immunology ,Adrenergic ,Autoimmunity ,CD8-Positive T-Lymphocytes ,ddc:616.07 ,Peripheral Nerve Injuries / pathology ,Article ,Inflammation / pathology ,Interferon-gamma ,03 medical and health sciences ,Adrenergic Agents ,0302 clinical medicine ,Immune system ,Neuroinflammation ,Peripheral Nerve Injuries ,Antigens / immunology ,Animals ,Immunology and Allergy ,Medicine ,Cytotoxic T cell ,Antigens ,Lymph node ,Inflammation ,Denervation ,business.industry ,Axotomy ,Lymph Nodes / pathology ,Sciatic Nerve ,Interferon-gamma / metabolism ,Mice, Inbred C57BL ,Sciatic Nerve / pathology ,CD8-Positive T-Lymphocytes / immunology ,030104 developmental biology ,medicine.anatomical_structure ,Peripheral nerve injury ,Lymph Nodes ,Sciatic nerve ,business ,Sciatic Nerve / immunology ,030217 neurology & neurosurgery ,Adrenergic Agents / metabolism ,Signal Transduction ,Sensory nerve - Abstract
This study shows loss of sympathetic innervation to the popliteal lymph node to induce IFN-γ expression in CD8 T cells, causing expansion. This is rescued by β2 adrenergic receptor agonists, demonstrating the pro-inflammatory effect of loss of direct adrenergic input., Peripheral nerve injury can cause debilitating disease and immune cell–mediated destruction of the affected nerve. While the focus has been on the nerve-regenerative response, the effect of loss of innervation on lymph node function is unclear. Here, we show that the popliteal lymph node (popLN) receives direct neural input from the sciatic nerve and that sciatic denervation causes lymph node expansion. Loss of sympathetic, adrenergic tone induces the expression of IFN-γ in LN CD8 T cells, which is responsible for LN expansion. Surgery-induced IFN-γ expression and expansion can be rescued by β2 adrenergic receptor agonists but not sensory nerve agonists. These data demonstrate the mechanisms governing the pro-inflammatory effect of loss of direct adrenergic input on lymph node function.
- Published
- 2021