Acute in vivo exposure to interferon-γ enables resident brain dendritic cells to become effective antigen presenting cells

被引:67
作者
Gottfried-Blackmore, Andres [2 ]
Kaunzner, Ulrike W. [2 ]
Idoyaga, Juliana [1 ]
Felger, Judit C. [2 ]
McEwen, Bruce S. [2 ]
Bulloch, Karen [1 ]
机构
[1] Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10065 USA
[2] Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10065 USA
关键词
CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; COLONY-STIMULATING FACTOR; IFN-GAMMA; CLASS-II; IMMUNE INVASION; CHOROID-PLEXUS; T-H-17; CELLS; MOUSE-BRAIN; MICROGLIA;
D O I
10.1073/pnas.0911509106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Dendritic cells (DC) are the professional antigen presenting cells (APC) that bridge the innate and adaptive immune system. Previously, in a CD11c/EYFP transgenic mouse developed to study DC functions, we anatomically mapped and phenotypically characterized a discrete population of EYFP+ cells within the microglia that we termed brain dendritic cells (bDC). In this study, we advanced our knowledge of the function of these cells in the CD11c/EYFP transgenic mouse and its chimeras, using acute stimuli of stereotaxically inoculated IFN gamma or IL-4 into the CNS. The administration of IFN gamma increased the number of EYFP+ bDC but did not recruit peripheral DC into the CNS. IFN gamma, but not IL-4, upregulated the expression levels of major histocompatibility class II (MHC-II). In addition, IFN gamma-activated EYFP(+)bDC induced antigen-specific naive CD4 T cells to proliferate and secrete Th1/Th17 cytokines. Activated bDC were also able to stimulate naive CD8 T cells. Collectively, these data reveal the Th1 cytokine IFN gamma, but not the Th2 cytokine IL4, induces bDC to up-regulate MHC-II and become competent APC.
引用
收藏
页码:20918 / 20923
页数:6
相关论文
共 45 条
  • [1] Aloisi F, 1999, EUR J IMMUNOL, V29, P2705, DOI 10.1002/(SICI)1521-4141(199909)29:09<2705::AID-IMMU2705>3.0.CO
  • [2] 2-1
  • [3] Functional maturation of adult mouse resting microglia into an APC is promoted by granulocyte-macrophage colony-stimulating factor and interaction with Th1 cells
    Aloisi, F
    De Simone, R
    Columba-Cabezas, S
    Penna, G
    Adorini, L
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 164 (04) : 1705 - 1712
  • [4] Aloisi F, 1998, J IMMUNOL, V160, P4671
  • [5] Glia-T cell dialogue
    Aloisi, F
    Serafini, B
    Adorini, L
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 2000, 107 (02) : 111 - 117
  • [6] CNS myeloid DCs presenting endogenous myelin peptides 'preferentially' polarize CD4+ TH-17 cells in relapsing EAE
    Bailey, Samantha L.
    Schreiner, Bettina
    McMahon, Eileen J.
    Miller, Stephen D.
    [J]. NATURE IMMUNOLOGY, 2007, 8 (02) : 172 - 180
  • [7] Neonatal and adult microglia cross-present exogenous antigens
    Beauvillain, Celine
    Donnou, Sabrina
    Jarry, Ulrich
    Scotet, Mari
    Gascan, Hugues
    Delneste, Yves
    Guermonprez, Pierre
    Jeannin, Pascale
    Couez, Dominique
    [J]. GLIA, 2008, 56 (01) : 69 - 77
  • [8] CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain
    Bulloch, Karen
    Miller, Melinda M.
    Gal-Toth, Judit
    Milner, Teresa A.
    Gottfried-Blackmore, Andres
    Waters, Elizabeth M.
    Kaunzner, Ulrike W.
    Liu, Kang
    Lindquist, Randall
    Nussenzweig, Michel C.
    Steinman, Ralph M.
    McEwen, Bruce S.
    [J]. JOURNAL OF COMPARATIVE NEUROLOGY, 2008, 508 (05) : 687 - 710
  • [9] Activation of microglia by aggregated β-amyloid or lipopolysaccharide impairs MHC-II expression and renders them cytotoxic whereas IFN-γ and IL-4 render them protective
    Butovsky, O
    Talpalar, AE
    Ben-Yaakov, K
    Schwartz, M
    [J]. MOLECULAR AND CELLULAR NEUROSCIENCE, 2005, 29 (03) : 381 - 393
  • [10] Glatiramer acetate fights against Alzheimer's disease by inducing dendritic-like microglia expressing insulin-like growth factor 1
    Butovsky, Oleg
    Koronyo-Hamaoui, Maya
    Kunis, Gilad
    Ophir, Eran
    Landa, Gennady
    Cohen, Hagit
    Schwartz, Michal
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (31) : 11784 - 11789