IL-15 and IL-15R alpha gene deletion: effects on T lymphocyte trafficking and the microglial and neuronal responses to facial nerve axotomy.
IL-15 is a potent T cell chemoattractant, and this cytokine and its unique alpha subunits, IL-15R alpha, can modify immune cell expression of several T cell chemokines and their receptors. Facial nerve axotomy in mice leads to T cell migration across an intact blood-brain-barrier (BBB), and under certain conditions T cells can provide neuroprotection to injured neurons in the facial motor nucleus (FMN). Although chemokines and chemoattractant cytokines are thought to be responsible for T cell migration to the injured cell bodies, data addressing this question are lacking. This study tested the hypothesis that T cell homing to the axotomized FMN would be impaired in knockout (KO) mice with the IL-15 and IL-15R alpha genes deleted, and sought to determine if microglial responsiveness and motoneuron death are affected. Both IL-15KO and IL-15R alpha KO mice exhibited a marked reduction in CD3(+) T cells and had fewer MHC2(+) activated microglia in the injured FMN than their respective WT controls at day 14 post-axotomy. Although there was a relative absence of T cell recruitment into the axotomized FMN in both knockout strains, IL-15R alpha KO mice had five times more motoneuron death (characterized by perineuronal microglial clusters engulfing dead motoneurons) than their WT controls, whereas dead neurons in IL-15KO did not differ from their WT controls. Further studies are needed to dissect the mechanisms that underlie these observations (e.g., central vs. peripheral immune contributions).
Huang
Zhi
Z
McKnight Brain Institute, University of Florida, Gainesville, FL 32608, USA.
Ha
Grace K
GK
Petitto
John M
JM
D000818:Animals; D019771:Axotomy; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D005154:Facial Nerve / Q000276:immunology / Q000378:metabolism; D020220:Facial Nerve Injuries / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005911:Gliosis / Q000235:genetics / Q000276:immunology*; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D053720:Interleukin-15 Receptor alpha Subunit / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009046:Motor Neurons / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit