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Blood, 15 January 2001, Vol. 97, No. 2, pp. 473-482
IMMUNOBIOLOGY
The soluble murine type I interferon receptor Ifnar-2 is present
in serum, is independently regulated, and has both agonistic and
antagonistic properties
Matthew P. Hardy,
Catherine
M. Owczarek,
Suzana Trajanovska,
Xiang Liu,
Ismail Kola, and
Paul J. Hertzog
From the Center for Functional Genomics and Human
Disease, Monash Institute of Reproduction and Development, Monash
University, Clayton, Victoria, Australia.
The ability to modify responses to type I interferons (IFNs) could
alter processes such as hematopoiesis and immunity, which involve
endogenous IFNs and responses to exogenous IFNs. The data presented
here support a significant role for a recently identified soluble
isoform of the murine type I IFN receptor, muIfnar-2a, as an efficient
regulator of IFN responses. The messenger RNA (mRNA) transcript
encoding muIfnar-2a is generally more abundant than that encoding the
transmembrane isoform, muIfnar-2c. Furthermore, the ratio of
muIfnar-2a:2c transcripts varied from more than 10:1 in the
liver and other organs to less than 1:1 in bone-marrow macrophages,
indicating independent regulation of the 2 transcripts encoding
receptor isoforms and suggesting that the soluble muIfnar-2a levels are
biologically relevant in some organs. Western blot analysis showed that
soluble muIfnar-2 was present at high levels in murine serum and other
biologic fluids and bound type I IFN. Recombinant muIfnar-2a
competitively inhibited the activity of both IFN and  in reporter
assays using the L929 cell line and in antiproliferative and antiviral
assays using primary cells. Surprisingly, using primary thymocytes from
Ifnar-2 / mice, recombinant muIfnar-2a
formed a complex with IFN or and muIfnar-1 at the cell
surface and transmitted an antiproliferative signal. These data
indicate potential dual actions of soluble muIfnar-2 and imply that a
signal can be transduced through the Ifnar-1 chain of the receptor
complex in the absence of the cytoplasmic domain of Ifnar-2. Therefore,
our results suggest that soluble Ifnar-2 is an important regulator of
endogenous and systemically administered type I IFN.
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