Differential expression and function of human IL-12Rβ2 polymorphic variants

The receptor for interleukin-12, formed by IL-12R beta 1 and IL-12R beta 2, mediates the type I immune responses of various types of lymphocytes. Polymorphisms in IL12RB2, the gene encoding IL-12R beta 2, were reported to be associated with several immune related diseases, such as Crohn's disease. Because the 1123R 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-12R beta 2 in immune diseases, we investigated the functional consequences of thirteen amino acid substitutions in IL-12R beta 2. We developed a model with retroviral expression of IL-12R beta 2 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-121202 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. (C) 2013 Elsevier Ltd. All rights reserved.