Cellular Sources and Neuroprotective Roles of Interleukin-10 in the Facial Motor Nucleus after Axotomy

Elizabeth M. Runge; Deborah O. Setter; Abhirami K. Iyer; Eric J. Regele; Felicia M. Kennedy; Virginia M. Sanders; Kathryn J. Jones

doi:10.3390/cells11193167

Cellular Sources and Neuroprotective Roles of Interleukin-10 in the Facial Motor Nucleus after Axotomy

Elizabeth M. Runge, Deborah O. Setter, Abhirami K. Iyer, Eric J. Regele, Felicia M. Kennedy, Virginia M. Sanders, Kathryn J. Jones

Department of Psychiatry

Research output: Contribution to journal › Article › peer-review

Abstract

Facial motoneuron (FMN) survival is mediated by CD4+ T cells in an interleukin-10 (IL-10)-dependent manner after facial nerve axotomy (FNA), but CD4+ T cells themselves are not the source of this neuroprotective IL-10. The aims of this study were to (1) identify the temporal and cell-specific induction of IL-10 expression in the facial motor nucleus and (2) elucidate the neuroprotective capacity of this expression after axotomy. Immunohistochemistry revealed that FMN constitutively produced IL-10, whereas astrocytes were induced to make IL-10 after FNA. Il10 mRNA co-localized with microglia before and after axotomy, but microglial production of IL-10 protein was not detected. To determine whether any single source of IL-10 was critical for FMN survival, Cre/Lox mouse strains were utilized to selectively knock out IL-10 in neurons, astrocytes, and microglia. In agreement with the localization data reflecting concerted IL-10 production by multiple cell types, no single cellular source of IL-10 alone could provide neuroprotection after FNA. These findings suggest that coordinated neuronal and astrocytic IL-10 production is necessary for FMN survival and has roles in neuronal homeostasis, as well as neuroprotective trophism after axotomy.

Original language	English
Article number	3167
Journal	Cells
Volume	11
Issue number	19
DOIs	https://doi.org/10.3390/cells11193167
State	Published - Oct 2022

Keywords

CD4+ T cell
IL-10
astrocyte
axotomy
facial nerve
motoneuron
nerve injury
neuroprotection

Access to Document

10.3390/cells11193167

Cite this

@article{33a7c09addeb42308892f6bfa46de9fb,

title = "Cellular Sources and Neuroprotective Roles of Interleukin-10 in the Facial Motor Nucleus after Axotomy",

abstract = "Facial motoneuron (FMN) survival is mediated by CD4+ T cells in an interleukin-10 (IL-10)-dependent manner after facial nerve axotomy (FNA), but CD4+ T cells themselves are not the source of this neuroprotective IL-10. The aims of this study were to (1) identify the temporal and cell-specific induction of IL-10 expression in the facial motor nucleus and (2) elucidate the neuroprotective capacity of this expression after axotomy. Immunohistochemistry revealed that FMN constitutively produced IL-10, whereas astrocytes were induced to make IL-10 after FNA. Il10 mRNA co-localized with microglia before and after axotomy, but microglial production of IL-10 protein was not detected. To determine whether any single source of IL-10 was critical for FMN survival, Cre/Lox mouse strains were utilized to selectively knock out IL-10 in neurons, astrocytes, and microglia. In agreement with the localization data reflecting concerted IL-10 production by multiple cell types, no single cellular source of IL-10 alone could provide neuroprotection after FNA. These findings suggest that coordinated neuronal and astrocytic IL-10 production is necessary for FMN survival and has roles in neuronal homeostasis, as well as neuroprotective trophism after axotomy.",

keywords = "CD4+ T cell, IL-10, astrocyte, axotomy, facial nerve, motoneuron, nerve injury, neuroprotection",

author = "Runge, {Elizabeth M.} and Setter, {Deborah O.} and Iyer, {Abhirami K.} and Regele, {Eric J.} and Kennedy, {Felicia M.} and Sanders, {Virginia M.} and Jones, {Kathryn J.}",

note = "Funding Information: This research was funded by the National Institutes of Health, National Institute of Neurologic Disorders and Stroke, R01 grant number NS40433 (V.M.S. and K.J.J.). Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = oct,

doi = "10.3390/cells11193167",

language = "English",

volume = "11",

journal = "Cells",

issn = "2073-4409",

number = "19",

}

TY - JOUR

T1 - Cellular Sources and Neuroprotective Roles of Interleukin-10 in the Facial Motor Nucleus after Axotomy

AU - Runge, Elizabeth M.

AU - Setter, Deborah O.

AU - Iyer, Abhirami K.

AU - Regele, Eric J.

AU - Kennedy, Felicia M.

AU - Sanders, Virginia M.

AU - Jones, Kathryn J.

N1 - Funding Information: This research was funded by the National Institutes of Health, National Institute of Neurologic Disorders and Stroke, R01 grant number NS40433 (V.M.S. and K.J.J.). Publisher Copyright: © 2022 by the authors.

PY - 2022/10

Y1 - 2022/10

N2 - Facial motoneuron (FMN) survival is mediated by CD4+ T cells in an interleukin-10 (IL-10)-dependent manner after facial nerve axotomy (FNA), but CD4+ T cells themselves are not the source of this neuroprotective IL-10. The aims of this study were to (1) identify the temporal and cell-specific induction of IL-10 expression in the facial motor nucleus and (2) elucidate the neuroprotective capacity of this expression after axotomy. Immunohistochemistry revealed that FMN constitutively produced IL-10, whereas astrocytes were induced to make IL-10 after FNA. Il10 mRNA co-localized with microglia before and after axotomy, but microglial production of IL-10 protein was not detected. To determine whether any single source of IL-10 was critical for FMN survival, Cre/Lox mouse strains were utilized to selectively knock out IL-10 in neurons, astrocytes, and microglia. In agreement with the localization data reflecting concerted IL-10 production by multiple cell types, no single cellular source of IL-10 alone could provide neuroprotection after FNA. These findings suggest that coordinated neuronal and astrocytic IL-10 production is necessary for FMN survival and has roles in neuronal homeostasis, as well as neuroprotective trophism after axotomy.

AB - Facial motoneuron (FMN) survival is mediated by CD4+ T cells in an interleukin-10 (IL-10)-dependent manner after facial nerve axotomy (FNA), but CD4+ T cells themselves are not the source of this neuroprotective IL-10. The aims of this study were to (1) identify the temporal and cell-specific induction of IL-10 expression in the facial motor nucleus and (2) elucidate the neuroprotective capacity of this expression after axotomy. Immunohistochemistry revealed that FMN constitutively produced IL-10, whereas astrocytes were induced to make IL-10 after FNA. Il10 mRNA co-localized with microglia before and after axotomy, but microglial production of IL-10 protein was not detected. To determine whether any single source of IL-10 was critical for FMN survival, Cre/Lox mouse strains were utilized to selectively knock out IL-10 in neurons, astrocytes, and microglia. In agreement with the localization data reflecting concerted IL-10 production by multiple cell types, no single cellular source of IL-10 alone could provide neuroprotection after FNA. These findings suggest that coordinated neuronal and astrocytic IL-10 production is necessary for FMN survival and has roles in neuronal homeostasis, as well as neuroprotective trophism after axotomy.

KW - CD4+ T cell

KW - IL-10

KW - astrocyte

KW - axotomy

KW - facial nerve

KW - motoneuron

KW - nerve injury

KW - neuroprotection

UR - http://www.scopus.com/inward/record.url?scp=85139757160&partnerID=8YFLogxK

U2 - 10.3390/cells11193167

DO - 10.3390/cells11193167

M3 - Article

C2 - 36231129

AN - SCOPUS:85139757160

VL - 11

JO - Cells

JF - Cells

SN - 2073-4409

IS - 19

M1 - 3167

ER -

Cellular Sources and Neuroprotective Roles of Interleukin-10 in the Facial Motor Nucleus after Axotomy

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this