Several studies have indicated that IL-17A, known as the hallmark cytokine of the T helper 17 (Th17) cell subset, plays significant roles in protective immune responses against pathogens, but is also involved in promoting inflammatory pathology in autoimmune diseases. As a leading expert in drug discovery, Creative Biolabs has established a Magic™ “humanized” mouse model platform for the development and evaluation of new immunotherapies. Currently, we can provide you with the humanized IL-17A knock-in mouse models and full professional technical support to facilitate your drug discovery studies.

Fundamental information of IL-17A

IL-17A, commonly referred to as IL-17, is a member of the interleukin 17 (IL-17) cytokine family, which including IL-17A, IL-17B, IL-17C, IL-17D, IL-17E (also called IL-25) and IL-17F. Generally, IL-17 family cytokines mediate the biological functions by surface receptors on target cells. Functional receptors of IL-17 family cytokines usually exit in the heterodimers form, with IL-17RA as a common subunit. The major source of IL-17A is a type of specialized T cells called Th17 cells, in various types of adaptive immunity. IL-17A derived from innate and adaptive sources may play a role in response to pathogen invasion at different phase and location of infection. It was mainly expressed by activated CD4+ (cluster of differentiation 4+) T cells, as well as several types of innate immune cells such as γδT.

Functions of IL-17A signaling

As mentioned before, IL-17A is involved in the protective process of host defense against certain pathogens at epithelial and mucosal barriers. It has shown great importance for the elimination of extracellular bacteria Citrobacter. rodentiumStaphylococcus aureus and Klebsiella pneumoniae, which infect the colon, skin and lung, respectively. Research suggests that IL-17A also stimulate the production of pro-inflammatory cytokine and chemokine upon Klebsiella pneumoniae challenge. What's more, IL-17A also plays a role in fungal infection in addition to bacterial immunity. IL-17A mediates the immunological function by inducing anti-pathogenic peptide, pro-inflammatory cytokine and chemokine secretion by responder cells. Subsequently, the release of these pro-inflammatory molecules activates the recruitment of innate immune cells to the site of infection and clearance of the pathogen.

Magic™ Humanized IL-17A Immune Checkpoint Knock-In Mice Fig.1. IL-17 Family Signaling Pathways. (Gaffen, 2009)

The Clinical Significance of IL-17A

Previous studies on IL-17A has emerged its significant importance in the protective inflammation during pathogen infection and chronic inflammation related to autoimmune diseases. Accordingly, further investigation of the generation and regulation of IL-17A expression, as well as the signaling mechanisms, may provide novel approaches for modulating the immune system in infectious and inflammatory diseases, in order to defend against these diseases.

Development of Humanized IL-17A Knock-In Mice

For the sake of discovering and further optimizing associated immunotherapies, scientists in Creative Biolabs make every effort to develop an array of well-validated Magic™ humanized mouse models for in vivo efficacy evaluation of novel agents, including IL-17A KI mouse, which is generated via Cas9-mediated homologous recombination. Each of our Magic™ humanized IL-17A KI mouse models is guaranteed to have fully humanized IL17A gene with uncompromised immune systems, and thus could be used as an ideal tool for immunology studies. Please feel free to contact us for more details.

Creative Biolabs also offers other various Humanized Mouse Models you may be interested in:

Reference

  1. Gaffen, S. L. Structure and signalling in the IL-17 receptor superfamily. Nature Reviews Immunology. 2009, 9(8):556.

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