Regulation of the germinal center response by microRNA-155.
MicroRNAs are small RNA species involved in biological control at multiple levels. Using genetic deletion and transgenic approaches, we show that the evolutionarily conserved microRNA-155 (miR-155) has an important role in the mammalian immune system, specifically in regulating T helper cell differentiation and the germinal center reaction to produce an optimal T cell-dependent antibody response. miR-155 exerts this control, at least in part, by regulating cytokine production. These results also suggest that individual microRNAs can exert critical control over mammalian differentiation processes in vivo.
Thai
To-Ha
TH
CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA.
Calado
Dinis Pedro
DP
Casola
Stefano
S
Ansel
K Mark
KM
Xiao
Changchun
C
Xue
Yingzi
Y
Murphy
Andrew
A
Frendewey
David
D
Valenzuela
David
D
Kutok
Jeffery L
JL
Schmidt-Supprian
Marc
M
Rajewsky
Nikolaus
N
Yancopoulos
George
G
Rao
Anjana
A
Rajewsky
Klaus
K
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D018858:Germinal Center / Q000276:immunology*; D007074:Immunoglobulin G / Q000032:analysis; D008213:Lymphocyte Activation; D008233:Lymphotoxin-alpha / Q000096:biosynthesis; D053308:Lymphotoxin-beta / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009596:Nitrophenols / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology; D010648:Phenylacetates; D027041:Somatic Hypermutation, Immunoglobulin; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007074:Immunoglobulin G; C505887:Ltb protein, mouse; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D035683:MicroRNAs; D009596:Nitrophenols; D010648:Phenylacetates; D014409:Tumor Necrosis Factor-alpha; C026242:4-hydroxy-5-nitrophenyl acetic acid