title: IL-10 within the CNS is necessary for CD4+ T cells to mediate neuroprotection.
abstract: We have previously shown that immunodeficient mice exhibit significant facial motoneuron (FMN) loss compared to wild-type (WT) mice after a facial nerve axotomy. Interleukin-10 (IL-10) is known as a regulatory cytokine that plays an important role in maintaining the anti-inflammatory environment within the central nervous system (CNS). IL-10 is produced by a number of different cells, including Th2 cells, and may exert an anti-apoptotic action on neurons directly. In the present study, the role of IL-10 in mediating neuroprotection following facial nerve axotomy in Rag-2- and IL-10-deficient mice was investigated. Results indicate that IL-10 is neuroprotective, but CD4+ T cells are not the requisite source of IL-10. In addition, using real-time PCR analysis of laser microdissected brainstem sections, results show that IL-10 mRNA is constitutively expressed in the facial nucleus and that a transient, significant reduction of IL-10 mRNA occurs following axotomy under immunodeficient conditions. Dual labeling immunofluorescence data show, unexpectedly, that the IL-10 receptor (IL-10R) is constitutively expressed by facial motoneurons, but is selectively induced in astrocytes within the facial nucleus after axotomy. Thus, a non-CD4+ T cell source of IL-10 is necessary for modulating both glial and neuronal events that mediate neuroprotection of injured motoneurons, but only with the cooperation of CD4+ T cells, providing an avenue of novel investigation into therapeutic approaches to prevent or reverse motoneuron diseases, such as amyotrophic lateral sclerosis (ALS).
authors: Department of Microbiology and Immunology, Loyola University Medical Center, Maywood, IL 60153, USA. neuroimmune@gmail.com
authors: Junping
authors: J
authors: Xin
authors: Derek A
authors: DA
authors: Wainwright
authors: Nichole A
authors: NA
authors: Mesnard
authors: Craig J
authors: CJ
authors: Serpe
authors: Virginia M
authors: VM
authors: Sanders
authors: Kathryn J
authors: KJ
authors: Jones
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002490:Central Nervous System / Q000276:immunology* / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D020220:Facial Nerve Injuries / Q000276:immunology / Q000503:physiopathology; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology / Q000502:physiology*; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D016753:Interleukin-10 / Q000276:immunology / Q000502:physiology*; D053709:Interleukin-10 Receptor alpha Subunit / Q000276:immunology / Q000502:physiology; D053710:Interleukin-10 Receptor beta Subunit / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000276:immunology / Q000502:physiology; D009474:Neurons / Q000276:immunology / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053709:Interleukin-10 Receptor alpha Subunit; D053710:Interleukin-10 Receptor beta Subunit; D016753:Interleukin-10