TY - JOUR
T1 - Interleukin (IL)-1 Receptor Signaling Is Required for Complete Taste Bud Regeneration and the Recovery of Neural Taste Responses following Axotomy
AU - Dong, Guangkuo
AU - Kogan, Schuyler
AU - Venugopal, Natasha
AU - Chang, Eddy
AU - He, Lianying
AU - Faal, Fama
AU - Shi, Yang
AU - McCluskey, Lynnette Phillips
N1 - Publisher Copyright:
Copyright © 2023 the authors.
PY - 2023/5/10
Y1 - 2023/5/10
N2 - Experimental or traumatic nerve injury causes the degeneration of associated taste buds. Unlike most sensory systems, the sectioned nerve and associated taste buds can then regenerate, restoring neural responses to tastants. It was previously unknown whether injury-induced immune factors mediate this process. The proinflammatory cytokines, interleukin (IL)-1a and IL-1b, and their requisite receptor are strongly expressed by anterior taste buds innervated by the chorda tympani nerve. We tested taste bud regeneration and functional recovery in mice lacking the IL-1 receptor. After axotomy, the chorda tympani nerve regenerated but was initially unresponsive to tastants in both WT and Il1r KO mice. In the absence of Il1r signaling, however, neural taste responses remained minimal even .8 weeks after injury in both male and female mice, whereas normal taste function recovered by 3 weeks in WT mice. Failed recovery was because of a 57.8% decrease in regenerated taste buds in Il1r KO compared with WT axotomized mice. Il1a gene expression was chronically dysregulated, and the subset of regenerated taste buds were reinnervated more slowly and never reached full volume as progenitor cell proliferation lagged in KO mice. Il1r signaling is thus required for complete taste bud regeneration and the recovery of normal taste transmission, likely by impairing taste progenitor cell proliferation. This is the first identification of a cytokine response that promotes taste recovery. The remarkable plasticity of the taste system makes it ideal for identifying injury-induced mechanisms mediating successful regeneration and recovery.
AB - Experimental or traumatic nerve injury causes the degeneration of associated taste buds. Unlike most sensory systems, the sectioned nerve and associated taste buds can then regenerate, restoring neural responses to tastants. It was previously unknown whether injury-induced immune factors mediate this process. The proinflammatory cytokines, interleukin (IL)-1a and IL-1b, and their requisite receptor are strongly expressed by anterior taste buds innervated by the chorda tympani nerve. We tested taste bud regeneration and functional recovery in mice lacking the IL-1 receptor. After axotomy, the chorda tympani nerve regenerated but was initially unresponsive to tastants in both WT and Il1r KO mice. In the absence of Il1r signaling, however, neural taste responses remained minimal even .8 weeks after injury in both male and female mice, whereas normal taste function recovered by 3 weeks in WT mice. Failed recovery was because of a 57.8% decrease in regenerated taste buds in Il1r KO compared with WT axotomized mice. Il1a gene expression was chronically dysregulated, and the subset of regenerated taste buds were reinnervated more slowly and never reached full volume as progenitor cell proliferation lagged in KO mice. Il1r signaling is thus required for complete taste bud regeneration and the recovery of normal taste transmission, likely by impairing taste progenitor cell proliferation. This is the first identification of a cytokine response that promotes taste recovery. The remarkable plasticity of the taste system makes it ideal for identifying injury-induced mechanisms mediating successful regeneration and recovery.
KW - chorda tympani nerve
KW - cytokine
KW - degeneration
KW - electrophysiology
KW - inflammation
KW - taste receptor cell
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U2 - 10.1523/JNEUROSCI.1355-22.2023
DO - 10.1523/JNEUROSCI.1355-22.2023
M3 - Article
C2 - 37015809
AN - SCOPUS:85159543135
SN - 0270-6474
VL - 43
SP - 3439
EP - 3455
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 19
ER -