title: Functional recovery and facial motoneuron survival are influenced by immunodeficiency in crush-axotomized mice.
abstract: Facial nerve axotomy is a well-described injury paradigm for peripheral nerve regeneration and facial motoneuron (FMN) survival. We have previously shown that CD4(+) T helper (Th) 1 and 2 effector subsets develop in the draining cervical lymph node, and that the IL-4/STAT-6 pathway of Th2 development is critical for FMN survival after transection axotomy. In addition, delayed behavioral recovery time in immunodeficient mice may be due to the absence of T and B cells. This study utilized a crush axotomy paradigm to evaluate FMN survival and functional recovery in WT, STAT-6 KO (impaired Th2 response), T-Bet KO (impaired Th1 response), and RAG-2 KO (lacking mature T and B cells) mice to elucidate the contributions of specific CD4(+) T cell subsets in motoneuron survival and recovery mechanisms. STAT-6 KO and RAG-2 KO mice exhibited decreased FMN survival after crush axotomy compared to WT, supporting a critical role for the Th2 effector cell in motoneuron survival before target reconnection. Long term FMN survival was sustained through 10 wpo after crush axotomy in both WT and RAG-2 KO mice, indicating that target derived neurotrophic support maintains FMN survival after target reconnection. In addition, RAG-2 KO mice exhibited delayed functional recovery compared to WT mice. Both STAT-6 and T-Bet KO mice exhibited partially delayed functional recovery compared to WT, though not to the extent of RAG-2 KO mice. Collectively, our findings indicate that both pro- and anti-inflammatory CD4(+) T cell responses contribute to optimal functional recovery from axotomy-induced facial paralysis, while FMN survival is supported by the anti-inflammatory Th2 response alone.
authors.affiliation: Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Medical Center, Maywood, IL 60153, USA. tbeahrs@yahoo.com
authors.forename: Taylor
authors.initials: T
authors.lastname: Beahrs
authors.forename: Lisa
authors.initials: L
authors.lastname: Tanzer
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Sanders
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Jones
mesh_terms: D000818:Animals; D019771:Axotomy / Q000379:methods; D001402:B-Lymphocytes / Q000502:physiology*; D001767:Blinking / Q000235:genetics / Q000502:physiology; D002452:Cell Count / Q000379:methods; D004268:DNA-Binding Proteins / Q000172:deficiency; D004195:Disease Models, Animal; D020220:Facial Nerve Injuries / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D007839:Functional Laterality; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000502:physiology*; D009068:Movement / Q000502:physiology; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology*; D050791:STAT Transcription Factors / Q000172:deficiency; D020825:T-Box Domain Proteins / Q000172:deficiency; D013601:T-Lymphocytes / Q000502:physiology*; D014738:Vibrissae / Q000294:innervation; D000098815:T-bet Transcription Factor
chemical_list: D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D050791:STAT Transcription Factors; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor