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Interleukin‐1 dysregulation is an intrinsic defect in macrophages from MRL autoimmune‐prone mice
Author(s) -
Levine Jerrold S.,
Pugh Barbara J.,
Hartwell Daqing,
Fitzpatrick John M.,
MarshakRothstein Ann,
Beller David I.
Publication year - 1993
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830231134
Subject(s) - biology , immunology , mouse strain , autoimmune disease , chimera (genetics) , autoimmunity , negative selection , cytokine , interleukin 17 , phenotype , interleukin 10 , genetics , gene , antibody , genome
Abstract Macrophages (Mϕ) from pre‐diseased autoimmune‐prone MRL mice (both MRL/+ and MRL/1pr) dramatically underproduce the cytokine interleukin‐1 (IL‐1) in comparison to Mϕ from a number of normal strains. In this study we show that IL‐1 dysregulation by MRL Mϕ is fully expressed at birth, and that this defect does not change with time or the development of disease. We also constructed adult irradiation chimeras (consisting of A/J → MRL and MRL → A/J mice), and show that Mϕ isolated from these chimeras display a pattern of IL‐1 production indistinguishable from that of the donor strain controls. Moreover, when we constructed a mixed chimera (A/J + MRL → A/J), the A/J and MRL Mϕ coexisting within the same animal retained their individual patterns of IL‐1 production when isolated by negative selection. Taken together, these results provide the first substantive evidence for an intrinsic defect (IL‐1 dysregulation) in Mϕ from MRL autoimmune‐prone mice.

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