Immunomodulation of EAE by alpha-fetoprotein involves elevation of immune cell apoptosis markers and the transcription factor FoxP3.
Alpha-fetoprotein (AFP) is an immunomodulatory glycoprotein associated with the normal growth of the mammalian fetus. Ws have shown that treatment with recombinant human AFP (rhAFP) reduced lymphocyte reactivity and the extent of neuroinflammation in mice with experimental autoimmune encephalomyelitis (EAE). In the present study we found involvement of AFP in immune cell apoptosis, attesting to its possible mechanism of action. AFP increased the expression of the Bax, Bid, Bad and ApaF genes in peripheral lymphocytes, together with an enhanced expression of Caspase-3, Fas, FasL and TRAIL among infiltrating immune cells. The induction of apoptosis markers was accompanied with an increased expression of Foxp3 in lymph node cells, as well as accumulation of CD4+Foxp3+ regulatory T cells in the CNS. Overall, these immunological alterations gave rise to a milder disease and accelerated remission rate. Our results suggest a new role for AFP in controlling the autoimmune inflammation associated with EAE.
Irony-Tur-Sinai
Michal
M
Laboratory of Neuroimmunology, Department of Neurology, the Agnes-Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Grigoriadis
Nikolaos
N
Tsiantoulas
Dimitrios
D
Touloumi
Olga
O
Abramsky
Oded
O
Brenner
Talma
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D015213:Neuroimmunomodulation / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000502:physiology*; D000509:alpha-Fetoproteins / Q000096:biosynthesis / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins