Soluble cytokine receptors play pivotal roles in health and disease. Signaling of the IL-6 (cytokine interleukin-6) via its ligand, sIL-6R (soluble IL-6 receptor) is causative for the proinflammatory properties of IL-6 and appears to be an attractive therapeutic target for many immune diseases. Anyway, research data suggest the potential utility of antibodies against the IL-6R as a novel molecular approach for targeting STAT3-dependent lung T cell survival and for the treatment of patients with allergic asthma in humans. Currently, scientists in Creative Biolabs has established well-characterized Magic™ “humanized” mouse models and are proud to offer the humanized IL-6R knock-in mouse models for those who are pursuing novel treatment for immune-related disorders.
The Significance of IL-6R Signaling Pathway
IL-6R (Interleukin 6 receptor), also known as CD126 (Cluster of Differentiation 126), is a typical type I cytokine receptor and act as a ligand binding protein of interleukin-6 (IL-6) and Ciliary neurotrophic factor. Functional IL6R is composed of two chains: IL-6R alpha (also called CD126, IL-6R-1, IL-6RA) in the strict sense (80 kDa, 468 amino acids; IL-6R gene is on chromosome 1q21) and the gp130 chain (also referred to as IL-6ST), which is the signal transducing chain. The human IL-6R plays a part in signal transduction of IL-6 which might be in relation to immune disease and various infectious disease. IL-6 is a cytokine secreted by human body upon trauma or infection to initiate the immune system response. IL-6 triggers inflammation in many diseases and it is partially responsible for fever.
The target cells of IL-6 is activated by IL-6R. The soluble form of this receptor, which is referred to as sIL-6R are highly expressed in the serum of healthy human bodies and is responsible for mediating inflammatory response in all human cells. IL-6 interacts with the IL-6R alpha, either membrane-bound (classical signaling) or in a soluble form (trans-signaling), and the IL-6/IL-6R complex associates with the signal transducer gp130, triggering its dimerization and consequent activation of the associated JAK kinases leading to intracellular signaling.
Fig.1. IL-6 signaling and trans-signaling. (Camporeale and Poli, 2013)
Development of Humanized IL6R Knock-In Mice
Specific blockades of IL-6 trans-signaling have the potential to be as effective as total IL-6 blockade and with reduced side effects. It has been reported that local targeting of IL-6R signaling could be a new approach for inducing Th2 T cell death in allergic airways via regulatory T cells. Moreover, another study shows that inhibition of IL-6/IL-6R signaling induces antiproliferative and apoptotic effects on breast cancer. Accordingly, using the humanized KI mouse model to make a better understanding of the IL-6signaling pathway will surely help to further optimize associated immune diseases. The Magic™ mouse models in Creative Biolabs has several advantageous features upon traditional mouse model: the mice carry a 100% human IL-6R gene which eliminates the human-to-mouse deviation related to drug targets. With extensive experience in constructing animal model and drug discovery, we now guarantee to offer the validated humanized IL6R KI mouse for our clients all over the world. Please feel free to contact us for more detailed information.
Creative Biolabs also offers other various Humanized Mouse Models you may be interested in:
Reference
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