Potential targets for autoimmune diseases—IL-5 drug screening cell model
Interleukin 5 (IL-5) is a member of Th2 (type 2 inflammatory factor) cytokine, consisting of 115 amino acids, and is a disulfide-linked dimeric glycoprotein. IL-5 is currently considered to be one of the key drivers of the Th2 pathway and plays an important role in autoimmune diseases.
The IL-5 receptor consists of a specific alpha chain (IL-5Rα) and a nonspecific beta chain. When IL-5 combines with IL-5Rα, it will combine with βc to form IL-5/IL-5Rα/βc complex, activate the intracellular JAK2 tyrosine kinase, and then activate the transcriptional activators STAT1, 3 and 5, making many Transcription of genes involved in the activation of eosinophil proliferation. JAK2 and β-chain combined JAK1 can simultaneously activate Raf-1 and NF-kB signaling pathways and affect the apoptosis process of eosinophils. The signaling pathway activated by IL-5 also includes two signaling pathways, phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), which can mediate the recruitment, maturation, differentiation and proliferation of eosinophils. The biological functions of IL-5 mainly include 1. Promote B cell differentiation, activate B cells to become immunoglobulin producing cells; 2.Promote the proliferation, differentiation, migration, activation and survival of eosinophils; 3.Promote basophils to release inflammatory mediators such as histamine and leukotrienes, thereby increasing the activity of basophils; 4.Promote IgA synthesis; 5.Synergy with ConA or IL-2 induces differentiation of killer T cell precursors (CTPp) into CTLs in the thymus. Current status of IL-5 drug research and development According to its principle, the design of IL-5 drugs can be roughly divided into two categories: targeting IL-5 and targeting IL-5 receptor. There are three IL-5 drugs currently on the market, Reslizumab, Benralizumab and Mepolizumab (Mepolizumab), among which Reslizumab and Mepolizumab are selective IL-5 antibodies, and Benralizumab is a selective IL-5Rα antibody. The most important of these, Mepolizumab, was approved for marketing in 2015. It is the first humanized monoclonal antibody targeting IL-5, which mainly binds to IL-5 and blocks IL-5 and eosinophil surface receptors. Combination, reduce eosinophil-mediated inflammatory response, existing indications include: hypereosinophilic syndrome (HES), chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic granulomatous Polyangiitis (EGPA). Since eosinophils are terminally differentiated granulocytes, they are part of the immune system. When stimulated by relevant internal and external factors, eosinophils will interact with various inflammatory cells and participate in the immune response by producing various pro-inflammatory mediators. Therefore, not only HES, CRSwNP, and EGPA, but also eosinophils are related to the occurrence of various autoimmune diseases. There are many clinical eosinophil-related diseases that require treatment, especially eosinophil-related asthma. Therefore, the development of IL-5 drugs for different indications has a high potential. IL-5 drug cell model For the development of IL-5 drugs and the quality control release requirements of existing recombinant IL-5 protein drugs, we have developed the hIL5 Effector Reporter Cell cell line, welcome to inquire. Part of the data is shown below: Figure 4. Dose Response of Recombinant Human IL5 in hlL5 Effector Reporter Cells (C9). Figure 5. Inhibition of hlL5-induced Reporter Activity by Abs in hlL5 Effector Reporter Cells (Clone9).
