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Loss of direct adrenergic innervation after peripheral nerve injury causes lymph node expansion through IFN-γ.

The Journal of experimental medicine

Authors: Chien-Sin Chen, Jasmin Weber, Stephan Jonas Holtkamp, Louise Madeleine Ince, Alba de Juan, Chen Wang, Lydia Lutes, Coline Barnoud, Burak Kizil, Sophia Martina Hergenhan, Johanna Salvermoser, Manuel Lasch, Elisabeth Deindl, Barbara Schraml, Dirk Baumjohann, Christoph Scheiermann

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.

© 2021 Chen et al.

PMID: 34086056

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