Disease relevance of Il5ra

• CONCLUSION: These findings indicate that IL-5Ralpha plays an important role in the development of antigen-induced airway eosinophilia and BHR in mice [1].
• However, retinyl acetate failed to induce resistance to CT toxicity in IL-5Ralpha(-/-) mice [2].
• An adenovirus vector (Ad) was then constructed that was inserted in an effective template sequence (Ad-IL-5Ralpha) [3].
• Investigators found that P-IL-5Ra-3 targeted at the sequence of CAG CTG CCT GGT TCG TCT T markedly suppressed IL-5Ralpha expression in B lymphoma cells in vitro [3].
• Abrogation of autoimmune disease in Lyn-deficient mice by the deletion of IL-5 receptor alpha chain gene [4].

High impact information on Il5ra

• The IL-5R alpha-/- mice produced basal levels of eosinophils, while their bone marrow cells failed to form eosinophilic colonies in response to IL-5 [5].
• The number of alpha beta T cell receptor-positive thymocytes tended to decrease in 3-week-old IL-5R alpha-/- mice, returning to normal by 6 weeks of age [5].
• We report the isolation of cDNA clones from cDNA libraries of human eosinophils by using murine IL-5 receptor alpha chain cDNA as a probe [6].
• Flow cytometry analysis revealed that CD38 ligation increased surface expression of the IL-5-receptor alpha chain on B cells [7].
• In addition, analysis using chimeric receptors which consist of the extracellular domain of IL-5R alpha and the cytoplasmic domain of beta c suggested that dimerization of the cytoplasmic domain of beta c may be an important step in activating the IL-5R complex and transducing intracellular growth signals [8].

Biological context of Il5ra

• There was no significant difference in serum antigen-specific IgE levels between wild-type and IL-5Ralpha KO mice after immunization nor antigen inhalation [1].
• An effective plasmid vector was selected that could express short hairpin RNA targeted at IL-5Ralpha (P-IL-5Ralpha) [3].
• Results reported here show that blocking of IL-5Ralpha expression through RNA interference can enhance effective treatment of asthma, and that bone marrow can be used as a key targeted organ in the treatment of asthmatic mice [3].
• We further demonstrate in vitro that ability to multiply persists in BALf CD34(+) cells but not CD34(-) cells, likely via autocrine IL-5 release and IL-5-induced up-regulation of IL-5R alpha [9].
• The second set of epitopes as well as the species specificity domain cluster around the loop 3-helix D region, which is predicted to engage the IL-5 receptor alpha-chain [10].

Anatomical context of Il5ra

• The transgenic mouse expressed IL-5R alpha ubiquitously, and the bone marrow cells formed various types of colonies, including multi-lineage colonies, in response to IL-5 [11].
• In IL-5Ralpha KO mice, there was little increase of eosinophils in bronchoalveolar lavage fluid (BALF) [1].
• Wild-type and heterozygous mice increased the IgA level and a number of IgA-containing cells in the mucosa in response to the vitamin A treatment, but not in IL-5Ralpha(-/-) mice [2].
• Both IL-5 and IL-5 receptor alpha chain (IL-5 Ralpha) were expressed in vitro in astrocytes, but not in neurons [12].
• Daily supplementation of retinyl acetate (1 mg/mouse) increased Th2 cytokine levels and a number of their positive cells in the small intestinal mucosa of IL-5Ralpha(-/-) mice, as observed in wild-type or IL-5Ralpha(+/-) mice [2].

Associations of Il5ra with chemical compounds

• In addition, transfectants expressing chimeric receptors which consist of the extracellular domain of IL-5R alpha and the cytoplasmic domain of beta c responded to IL-5 for proliferation and tyrosine phosphorylation of JAK1 [13].
• CD38 ligation on mouse B cells by CS/2, an anti-mouse CD38 mAb, induces proliferation, IL-5 receptor alpha chain expression and tyrosine phosphorylation of Bruton's tyrosine kinase [14].
• Mutational analysis revealed that one of the proline residues, particularly Pro352 and Pro355, in the membrane-proximal proline-rich sequence (Pro352-Pro353-X-Pro355) of the cytoplasmic domain of IL-5R alpha is required for cell proliferation, and for both JAK1 and JAK2 activation [13].
• METHODS: IL-5 receptor alpha-chain-deficient (IL-5Ralpha-/-) mice and IL-5Ralpha+/+ mice were contact sensitized with oxazolone hapten [15].

Physical interactions of Il5ra

• IL-5R alpha binds IL-5 with low affinity [16].

Regulatory relationships of Il5ra

• Multi-colony stimulating activity of interleukin 5 (IL-5) on hematopoietic progenitors from transgenic mice that express IL-5 receptor alpha subunit constitutively [11].
• Most OSM-expressing cells expressed IL-5 receptor alpha subunit, a marker for eosinophil lineage [17].
• In this study, we generated cDNAs of IL-5R alpha having various mutations in their cytoplasmic domains and examined the function of these mutants by expressing them in IL-3-dependent FDC-P1 cells [8].

Other interactions of Il5ra

• These results strongly suggest that the lineage specificity of IL-5 is mainly due to the restricted expression of IL-5R alpha [11].
• Eosinophil peroxidase activity in the sensitized and challenged IL-5Ralpha-/- mice was about 11 times less than that in immunized IL-5Ralpha+/+ mice [15].
• Regulation of IL-5R alpha, IL-3R alpha and GM-CSFR alpha expression in the developmental stage appears to be important for understanding the unique function of these cytokines on a particular cell type [18].
• With the mouse-specific IL5R tandem repeat sequence in recombinant inbred strains of mice, the Il5r gene was mapped to the distal part of mouse Chr 6 close to the Raf-1 locus [19].
• Culture of resting B cells with IL-4 induced expression of the IL-5R alpha-chain, while signaling through membrane Ig stimulated expression of the IL-5R beta-chain [20].

Analytical, diagnostic and therapeutic context of Il5ra

• We generated interleukin-5 receptor alpha chain (IL-5R alpha)-deficient (IL-5R alpha-/-) mice by gene targeting [5].
• Biochemical and functional characterization of soluble form of IL-5 receptor alpha (sIL-5R alpha). Development of ELISA system for detection of sIL-5R alpha [21].
• METHODS: We have designed a quantitative reverse transcriptase-polymerase chain reaction assay to detect transcripts encoding the transmembrane, soluble 1 and 2 forms of IL-5R alpha in two strains of wild-type (BALB/c and C57BL/6) and corresponding IL-5 gene-deleted mice [22].

References