Critical role of preproenkephalin in experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is an organ-specific autoimmune disease model used to investigate mechanisms involved in the activation of self-reactive T cells. Preproenkephalin (PPNK) is the gene that encodes the protein proenkephalin A that has been detected in the brain, adrenal cells and cells of the immune system. In this paper, whether PPNK plays a role in the development of EAE was investigated. PPNK-deficient and wild-type mice were immunized with the MOG(35-55) peptide and the development of EAE observed. Our results show that PPNK-deficient mice developed less severe clinical signs of disease than wild-type mice, and with lower incidence. MOG(35-55)-specific T cells from PPNK-deficient and wild-type mice produced IFNgamma and TNFalpha but no IL-4 or IL-10, indicative of a Th1 phenotype. However, the numbers of MOG(35-55)-specific IFNgamma-producing cells from immunized PPNK-deficient mice were largely reduced at early stages of disease. Interestingly, there was no difference in clinical signs or infiltrating mononuclear cells in the CNS between wild-type and PPNK-deficient mice at the later stage of disease. Our results suggest that PPNK accelerates the generation of autoimmune IFNgamma-producing T cells and MOG(35-55)-induced EAE.
Weir
Catherine
C
Malaghan Institute of Medical Research, Wellington South, New Zealand.
McNeill
Andrea
A
Hook
Sarah
S
Harvie
Marina
M
La Flamme
Anne Camille
AC
Le Gros
Graham
G
Bäckström
B Thomas
BT
D000818:Animals; D049109:Cell Proliferation; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004745:Enkephalins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D011498:Protein Precursors / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D004745:Enkephalins; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; C445081:myelin oligodendrocyte glycoprotein (35-55); D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; C033660:preproenkephalin