title: OCH-mediated shift of Th1 and Th2 cytokines by NKT cells in mice with aplastic anemia.
abstract: The immune-mediated destruction of bone marrow (BM) is the major cause of aplastic anemia (AA) in most patients. It has been shown that an imbalance of Th1 and Th2 cells is involved in immune-mediated destruction of BM in patients with AA. In the present study, we determined the role of NKT cells in regulating the balance of Th1 and Th2 cytokines. We found that the number of NKT cells from bone marrow mononuclear cells was lower in AA mice than normal mice. When treated with α-GalCer or its analog OCH, AA mice showed a significantly reduced capacity of NKT cell expansion. Furthermore, we found that the number of IFN-γ-producing NKT cells was higher in AA mice compared to normal counter-partners. However, OCH treatment inhibited IFN-γ production and enhanced IL-4 production by NKT cells in which we saw a balanced Th1- to Th2-type cytokines in AA mice. Interestingly, we observed that OCH treatment promoted hematopoietic cell growth, as indicated by increased colony counts in AA mice. Taken together, our results not only demonstrated a role of OCH in the maintenance of Th1/Th2 balance and recovery of hematopoietic cell growth, but also revealed a therapeutic potential of OCH in AA.
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji University, 389 Xincun Road, Shanghai, 200065, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Qiao
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Xie
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Jinqing
authors.initials: J
authors.lastname: Tang
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Shao
authors.forename: Fuxing
authors.initials: F
authors.lastname: Li
mesh_terms: D000741:Anemia, Aplastic / Q000097:blood* / Q000503:physiopathology; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D016207:Cytokines / Q000097:blood*; D005260:Female; D006017:Glycolipids / Q000494:pharmacology*; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D016207:Cytokines; D006017:Glycolipids; C501055:tetracosanoic acid 1-galactopyranosyloxy-3,4-dihydroxydec-2-yl amide; D015847:Interleukin-4; D007371:Interferon-gamma