Editors' ChoiceNEUROINFLAMMATION

Lymph nodes lose their nerve

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Science Signaling  15 Jun 2021:
Vol. 14, Issue 687, eabj9379
DOI: 10.1126/scisignal.abj9379

Loss of sciatic innervation of the popliteal lymph node causes IFN-γ–dependent lymph node expansion.

In addition to causing motor function problems, damage to peripheral nerves triggers immune cell infiltration and inflammation, which enables nerve regrowth and recovery. Lymph nodes are innervated by sensory and sympathetic nerves, and patients with nerve injuries can exhibit dysfunctional immune responses. Chen et al. generated a mouse model of peripheral nerve injury by surgically transecting the sciatic nerve at the hip and then examining the popliteal lymph node (popLN), which is located under the knee. The surgery resulted in popLN expansion, which was due to an increase in the numbers of lymphocytes, effects that were replicated in mice treated with phenol to block sciatic nerve function. The surgically induced increase in popLN cellularity depended on lymphocyte recruitment from the blood and signaling by the cytokine interferon-γ (IFN-γ) produced by CD8+ T cells. The sciatic nerve bundle consists of sensory, sympathetic, and motor neurons. Immunofluorescence staining revealed direct innervation of the popLN by sensory and sympathetic fibers. Treatment of denervated mice with the β2-adrenergic receptor (β2AR) agonist (and sympathetic nerve agonist) clenbuterol inhibited popLN expansion, whereas sensory nerve agonists had no effect. Clenbuterol reduced the numbers of IFN-γ–producing CD8+ T cells in the popLN of denervated mice, effects that were lost in β2AR-deficient mice. Together, these data suggest that peripheral nerve damage and loss of sympathetic tone result in lymph node expansion in an IFN-γ–dependent manner.

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