Disease relevance of IL10RB

• Given our results, which in some patients were in disagreement with their cytogenetic descriptions, trisomy for locus D21S13 through locus D21S58 is excluded from significant contribution to many Down syndrome features [1].

High impact information on IL10RB

• Thus, CRFB4 mutant mice recapitulate the phenotype of IL-10-deficient mice [2].
• These results demonstrate that the CRFB4 chain is part of the IL-10 receptor signaling complex [3].
• IL-10/-592 and IL10RB/c238 genotypes were tested for association with GVHD by multivariable analysis [4].
• A single nucleotide polymorphism (A/G) at cDNA position 238 of the IL-10 receptor beta gene (IL10RB/c238) was genotyped in 953 HC transplant recipients and their HLA-identical sibling donors [4].
• IL-22 acts via a heterodimeric receptor complex consisting of IL-22R1 and IL-10R2 [5].

Biological context of IL10RB

• IL-10R2 does not bind to cIL-10 or vIL-10 alone and its presence does not enhance the receptor-binding affinity of cIL-10 or vIL-10, but it is essential for both cIL-10- and vIL-10-mediated signal transduction and immune regulation [6].
• Because CRF2-4 exhibits ubiquitous expression, the tropism of IL-22 action appears to be dictated by the expression of IL-22R1 [7].
• Exons of the IFNAR1 and CRFB4 genes were also analyzed by SSCP and demonstrated no evidence of mutation [8].
• Recently, a gene causing the familial form of ALS (FALS) has been assigned to an interval of approximately 10 cM including the locus D21S58 on chromosome 21q22 [9].

Anatomical context of IL10RB

• The expression of IL-10R2 was ubiquitous whereas IL-10R1 was predominantly expressed on hematopoietic cells, including, T cells, B cells, NK cells, monocytes and dendritic cells [10].
• However, IL-10R1 (but not IL-10R2) mRNA and protein expression was substantially increased in neutrophils stimulated by LPS [11].
• IL-22 is produced by activated T cells and signals through a receptor complex consisting of IL-22R1 and IL-10R2 [12].
• Here, we demonstrate that intestinal epithelial cell (IEC) lines as well as murine and human colonic tissue express the IFN-lambda receptor subunits IL-28R and IL-10R2 [13].
• However, IL-10R1 and IL-10R2 are constitutively and ubiquitously expressed in all the B-cell lines included in our study [14].

Associations of IL10RB with chemical compounds

• The candidate region is approximately 4 Mb and contains the genes copper/zinc superoxide dismutase (CuZnSOD); the fourth member of the class II cytokine receptor family (CRF2-4); and the interferon-alpha receptor (IFNAR) [15].

Physical interactions of IL10RB

• In addition, IL-22 mediates inflammation and binds class II cytokine receptor heterodimers IL-22 RA1/CRF2-4 [16].
• First, we show that hepatic cell lines express the IFN-lambda receptor complex consisting of IFN-lambdaR1 (IL-28R1) and IL-10R2 [17].
• IL-22 is an IL-10 homologue that binds to and signals through the class II cytokine receptor heterodimer IL-22RA1/CRF2-4 [18].

Regulatory relationships of IL10RB

• The aim of this study is to identify potential target cells and associated biological activity of IL-22 by identifying cell types that specifically express high levels of IL-22R1 as the expression of IL-10R2 is ubiquitous [19].

Other interactions of IL10RB

• However, the co-expression of CRFB4, a transmembrane protein of previously unknown function belonging to the class II cytokine receptor family, together with the IL-10R1 chain renders hamster cells sensitive to IL-10 [3].
• However, in hamster cells both chains, CRF2-9 and IL-10R2, must be expressed to assemble the functional IL-TIF receptor complex [20].
• IL-10R2 is broadly expressed on a wide variety of tissues, whereas only a limited number of tissues express IL-20R1 [21].
• Temporal associations between interleukin 22 and the extracellular domains of IL-22R and IL-10R2 [22].
• IL-22 has measurable affinity for IL-22R-Fc homodimer and undetectable affinity for IL-10R2 [22].

Analytical, diagnostic and therapeutic context of IL10RB

• On binding to its cognate receptor (IL-22R1), which is associated to the interleukin-10 receptor 2 (IL-10R2), IL-22 promotes activation of signal transducer and activator of transcription (STAT) pathway and several other cellular responses [23].
• A full-length cDNA corresponding to a gene mapping to the D21S58 locus was cloned [24].
• Reverse transcriptase-polymerase chain reaction assay demonstrated that mouse liver expressed high levels of IL-10 receptor 2 (IL-10R2) but low levels of IL-10R1 [25].
• Finally, real time mRNA analyses and Western blot experiments demonstrated that the absence of any specific binding results from the absence of clear IL-10R1 (alpha chain) expression, whereas the IL-10R2 (beta chain) is strongly expressed [26].
• The expression of IL-10R1 but not IL-10R2 was augmented on monocytes cultured in the presence of RA synovial tissue (ST) cell culture supernatants [27].

References