IL-10 within the CNS is necessary for CD4+ T cells to mediate neuroprotection

Junping Xin, Derek A. Wainwright, Nichole A. Mesnard, Craig J. Serpe, Virginia M. Sanders, Kathryn J. Jones

Research output: Contribution to journalArticle

50 Citations (Scopus)

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).

Original languageEnglish (US)
Pages (from-to)820-829
Number of pages10
JournalBrain, Behavior, and Immunity
Volume25
Issue number5
DOIs
StatePublished - Jul 1 2011

Fingerprint

Interleukin-10
Central Nervous System
T-Lymphocytes
Axotomy
Motor Neurons
Facial Nerve
Interleukin-10 Receptors
Neuroprotection
Th2 Cells
Messenger RNA
Amyotrophic Lateral Sclerosis
Neuroglia
Astrocytes
Brain Stem
Fluorescent Antibody Technique
Real-Time Polymerase Chain Reaction
Lasers
Anti-Inflammatory Agents
Cell Count
Cytokines

Keywords

  • Axotomy
  • CD4 T cell
  • Facial motoneuron
  • Interleukin-10
  • Neuroprotection
  • Survival

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

IL-10 within the CNS is necessary for CD4+ T cells to mediate neuroprotection. / Xin, Junping; Wainwright, Derek A.; Mesnard, Nichole A.; Serpe, Craig J.; Sanders, Virginia M.; Jones, Kathryn J.

In: Brain, Behavior, and Immunity, Vol. 25, No. 5, 01.07.2011, p. 820-829.

Research output: Contribution to journalArticle

Xin, Junping ; Wainwright, Derek A. ; Mesnard, Nichole A. ; Serpe, Craig J. ; Sanders, Virginia M. ; Jones, Kathryn J. / IL-10 within the CNS is necessary for CD4+ T cells to mediate neuroprotection. In: Brain, Behavior, and Immunity. 2011 ; Vol. 25, No. 5. pp. 820-829.
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