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Interleukin-12 receptor beta 1 ( IL12RB1), interleukin-12 receptor beta 2 ( IL12RB2), and interferon gamma receptor 1 ( IFNGR1) perform important roles in the host defense against intracellular pathogens such as Mycobacteria. Several mutations within their genes have been confirmed as associated with increased susceptibility to mycobacterial infection. However, the association between mutations of the IL12RB1, IL12RB2, and IFNGR1 encoding genes and lepromatous leprosy has not been studied. This study screened for polymorphisms within IL12RB1, IL12RB2, and IFNGR1 encoding genes in the Korean populations using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) DNA sequencing assay, and an association study was performed using the missense mutations of 705 A/G (Q214R), 1196 G/C (G378R), 1637 G/A (A525T), and 1664 C/T (P534S) of the IL12RB1, 83 G/A (V14M), and 1443 T/C (L467P) for the IFNGR1 encoding genes. There were no differences in the genotype and allele frequencies of IL12RB1 and IFNGR1 genes between 93 lepromatous leprosy patients and 94 control subjects. In conclusion, missense mutations of 705 A/G (Q214R), 1196 G/C (G378R), 1637 G/A (A525T), 1664 C/T (P534S) of the IL12RB1, 83 G/A (V14 M), and 1443 T/C (L467P) of the IFNGR1 encoding genes have no association with the susceptibility to lepromatous leprosy in the Korean population.

Cell-mediated immunity (CMI) plays an essential role in human host defense against intracellular bacteria. Type-1 cytokines, particularly gamma interferon (IFN-gamma), interleukin-12 (IL-12), and IL-23, the major cytokines that regulate IFN-gamma production, are essential in CMI. This is illustrated by patients with unusual severe infections caused by poorly pathogenic mycobacteria and Salmonella species, in whom genetic deficiencies have been identified in several key genes in the type-1 cytokine pathway, including IL12RB1, the gene encoding the beta1 chain of the IL-12 and IL-23 receptors. Several mutations in IL12RB1 with deleterious effects on human IL-12R function have been identified, including nonsense and missense mutations. In addition, a number of coding IL12RB1 polymorphisms have been reported. In order to gain more insight into the effect that IL12RB1 mutations and genetic variations can have on IL-12Rbeta1 function, three approaches have been followed. First, we determined the degree of conservation at the variant amino acid positions in IL-12Rbeta1 between different species, using known deleterious mutations, known variations in IL-12Rbeta1, as well as novel coding variations that we have identified at position S74R and R156H. Second, we analyzed the potential impact of these amino acid variations on the three-dimensional structure of the IL-12Rbeta1 protein. Third, we analyzed the putative functions of different IL-12Rbeta1 domains, partly based on their homology with gp130, and analyzed the possible effects of the above amino acid variations on the function of these domains. Based on these analyses, we propose an integrated model of IL-12Rbeta1 structure and function. This significantly enhances our molecular understanding of the human IL-12 and IL-23 systems.

Interleukin (IL)-13 is a pleiotropic immune regulatory cytokine that shares structural and biological characteristics with IL-4. The receptor for IL-13 is comprised of the IL-4 receptor alpha (IL-4Ralpha) subunit and a low-affinity IL-13-binding subunit, IL-13Ralpha1. An additional receptor, IL-13Ralpha2, binds to IL-13 with high affinity, but lacks the cytoplasmic domain for signaling. In this study, we isolated the mouse IL-13Ralpha1 gene (Il13ra1) of approximately 56 kb that spans the entire coding region. The mouse Il13ra1 gene is composed of 11 exons, and shows striking similarity in genomic structure to the previously reported class I cytokine receptor genes. Motifs characteristic of the cytokine receptor family are similarly organized on the genome, including conserved cysteines, a WSxWS motif, and Box1, indicating closely related genetic evolution of the cytokine receptor superfamily. Alternative mRNA splicings were demonstrated to generate variant transcripts that encode soluble IL-13Ralpha1. The mouse Ill13ra1 gene was mapped to the proximal region of the mouse X chromosome, and was closely linked to the DXPas3 locus by interspecific backcross analysis. Il13ra1 mRNA was co-expressed with I14ra mRNA in mouse myeloid and natural killer cells on which IL-13 has been known to act, whereas the Il13ra2 mRNA was not detected in these cells, indicating that IL-13Ralpha1 is the major component of the IL-13 receptor complex in lymphohematopoietic cells.