title: Exacerbation of facial motoneuron loss after facial nerve axotomy in CCR3-deficient mice.
abstract: We have previously demonstrated a neuroprotective mechanism of FMN (facial motoneuron) survival after facial nerve axotomy that is dependent on CD4(+) Th2 cell interaction with peripheral antigen-presenting cells, as well as CNS (central nervous system)-resident microglia. PACAP (pituitary adenylate cyclase-activating polypeptide) is expressed by injured FMN and increases Th2-associated chemokine expression in cultured murine microglia. Collectively, these results suggest a model involving CD4(+) Th2 cell migration to the facial motor nucleus after injury via microglial expression of Th2-associated chemokines. However, to respond to Th2-associated chemokines, Th2 cells must express the appropriate Th2-associated chemokine receptors. In the present study, we tested the hypothesis that Th2-associated chemokine receptors increase in the facial motor nucleus after facial nerve axotomy at timepoints consistent with significant T-cell infiltration. Microarray analysis of Th2-associated chemokine receptors was followed up with real-time PCR for CCR3, which indicated that facial nerve injury increases CCR3 mRNA levels in mouse facial motor nucleus. Unexpectedly, quantitative- and co-immunofluorescence revealed increased CCR3 expression localizing to FMN in the facial motor nucleus after facial nerve axotomy. Compared with WT (wild-type), a significant decrease in FMN survival 4 weeks after axotomy was observed in CCR3(-/-) mice. Additionally, compared with WT, a significant decrease in FMN survival 4 weeks after axotomy was observed in Rag2(-/-) (recombination activating gene-2-deficient) mice adoptively transferred CD4(+) T-cells isolated from CCR3(-/-) mice, but not in CCR3(-/-) mice adoptively transferred CD4(+) T-cells derived from WT mice. These results provide a basis for further investigation into the co-operation between CD4(+) T-cell- and CCR3-mediated neuroprotection after FMN injury.
authors.affiliation: Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Maywood, IL 60153, U.S.A. Derekwainwright@hotmail.com
authors.forename: Derek A
authors.initials: DA
authors.lastname: Wainwright
authors.forename: Junping
authors.initials: J
authors.lastname: Xin
authors.forename: Nichole A
authors.initials: NA
authors.lastname: Mesnard
authors.forename: Taylor R
authors.initials: TR
authors.lastname: Beahrs
authors.forename: Christine M
authors.initials: CM
authors.lastname: Politis
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Sanders
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Jones