TY - JOUR
T1 - Unexpected role for the immunoproteasome subunit LMP2 in antiviral humoral and innate immune responses
AU - Hensley, Scott E.
AU - Zanker, Damien
AU - Dolan, Brian P.
AU - David, Alexandre
AU - Hickman, Heather D.
AU - Embry, Alan C.
AU - Skon, Cara N.
AU - Grebe, Kristie M.
AU - Griffin, Thomas A.
AU - Chen, Weisan
AU - Bennink, Jack R.
AU - Yewdell, Jonathan W.
PY - 2010/4/15
Y1 - 2010/4/15
N2 - Proteasomes are multisubunit proteases that initiate degradation of many Ags presented by MHC class I molecules. Vertebrates express alternate forms of each of the three catalytic proteasome subunits: standard subunits, and immunosubunits, which are constitutively expressed by APCs and are induced in other cell types by exposure to cytokines. The assembly of mixed proteasomes containing standard subunits and immunosubunits is regulated in a tissue specific manner. In this study, we report that the presence of mixed proteasomes in immune cells in LMP2-/- mice compromises multiple components that contribute to the generation of antiviral Ab responses, including splenic B cell numbers, survival and function of adoptively transferred B cells, Th cell function, and dendritic cell secretion of IL-6, TNF-α, IL-1β, and type I IFNs. These defects did not result from compromised overall protein degradation, rather they were associated with altered NF-κB activity. These findings demonstrate an important role for immunoproteasomes in immune cell function beyond their contribution to Ag processing.
AB - Proteasomes are multisubunit proteases that initiate degradation of many Ags presented by MHC class I molecules. Vertebrates express alternate forms of each of the three catalytic proteasome subunits: standard subunits, and immunosubunits, which are constitutively expressed by APCs and are induced in other cell types by exposure to cytokines. The assembly of mixed proteasomes containing standard subunits and immunosubunits is regulated in a tissue specific manner. In this study, we report that the presence of mixed proteasomes in immune cells in LMP2-/- mice compromises multiple components that contribute to the generation of antiviral Ab responses, including splenic B cell numbers, survival and function of adoptively transferred B cells, Th cell function, and dendritic cell secretion of IL-6, TNF-α, IL-1β, and type I IFNs. These defects did not result from compromised overall protein degradation, rather they were associated with altered NF-κB activity. These findings demonstrate an important role for immunoproteasomes in immune cell function beyond their contribution to Ag processing.
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U2 - 10.4049/jimmunol.0903003
DO - 10.4049/jimmunol.0903003
M3 - Article
C2 - 20228196
AN - SCOPUS:77952770300
SN - 0022-1767
VL - 184
SP - 4115
EP - 4122
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -