Increased levels of bioactive IL-16 correlate with disease activity during relapsing experimental autoimmune encephalomyelitis (EAE).
Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T-cell mediated disease, which resembles immunopathology of multiple sclerosis (MS). Interleukin (IL)-16 is a CD4+ cell-specific chemoattractant cytokine. In CD4+ T cells, production of bioactive IL-16 from constitutive pro-IL-16 requires cleavage by active caspase-3. We reported reversal of established relapsing disease by IL-16 neutralization. To better understand role(s) of IL-16 in regulation of relapsing EAE, we comparatively analyzed levels of IL-16, active caspase-3 and CD4 in mice with severe relapsing-remitting [(B6xSJL) F1], and low-relapsing (B6), disease. Elevated levels of IL-16 along with an increase in active-caspase-3 and CD4 levels correlated with stages of clinically active disease in both strains. CNS levels of bioactive IL-16 were notably higher in F1 compared to B6 mice at all stages, being most prominent during relapse. Similar patterns of regulation for IL-16 and active caspase-3 were observed in peripheral lymphoid organs, and in T cells isolated from lymph nodes following T-cell activation in vitro. IL-16 was co-immunoprecipitated with CD4 from CNS of relapsing mice. Our data suggest that caspase-3 mediated production of IL-16 by infiltrating CD4+ T cells, contributes to ongoing neuroinflammation by chemoattraction of additional waves of CD4+ T cells.
Skundric
Dusanka S
DS
Department of Neurology, Wayne State University School of Medicine, 421 East Canfield, 2226 Elliman Building, Detroit, MI 48201, USA. skundric@cmb.biosci.wayne.edu
Zhou
Weili
W
Cruikshank
William W
WW
Dai
Rujuan
R
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D053148:Caspase 3 / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019410:Interleukin-16 / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012008:Recurrence
D019410:Interleukin-16; D053148:Caspase 3