Differential expression and function of human IL-12RI22 polymorphic variants

The receptor for interleukin-12, formed by IL-12RI21 and IL-12RI22, mediates the type I immune responses of various types of lymphocytes. Polymorphisms in IL12RB2, the gene encoding IL-12RI22, were reported to be associated with several immune related diseases, such as Crohn's disease. Because...

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Published in:Molecular immunology 2013-12, Vol.56 (4), p.380-389
Main Authors: Paus, Roelof, Geilenkirchen, Marije, Riet, Sander, Dissel, Jaap, Vosse, Esther
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container_title Molecular immunology
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creator Paus, Roelof
Geilenkirchen, Marije
Riet, Sander
Dissel, Jaap
Vosse, Esther
description The receptor for interleukin-12, formed by IL-12RI21 and IL-12RI22, mediates the type I immune responses of various types of lymphocytes. Polymorphisms in IL12RB2, the gene encoding IL-12RI22, were reported to be associated with several immune related diseases, such as Crohn's disease. Because the IL23R and IL12RB2 genes are located in close proximity on the genome, the reported associations might also be attributable to linked polymorphisms in IL23R, which were found to be associated with immune related diseases as well. To clarify the role of IL-12RI22 in immune diseases, we investigated the functional consequences of thirteen amino acid substitutions in IL-12RI22. We developed a model with retroviral expression of IL-12RI22 in B cell lines. With the use of this model the expression and function of the variants was compared within the same genetic background. Four of the IL-12RI22 variants, N271Y, R313G, A604V and L808R showed reduced IL-12 responses compared to the wild type variant. Two of these are relatively common in some populations and may be used in future association studies to reveal a role for IL-12 in infectious and/or immune related diseases.
doi_str_mv 10.1016/j.molimm.2013.07.002
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title Differential expression and function of human IL-12RI22 polymorphic variants
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