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Blausen Medical

Blausen Medical

Medically accurate and informative 3D animations

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JAK-STAT Inhibition in IBD II

The gut must maintain immune homeostasis by tolerating beneficial bacteria and harmless food antigens, while inducing an effective inflammatory response against pathogenic microorganisms. When this balance is disrupted, diseases can occur, including inflammatory bowel disease, or IBD. IBD is characterized by upregulation of multiple proinflammatory cytokines that stimulate mucosal inflammation. The binding of cytokines to the receptor initiates a signaling cascade that regulates gene transcription in the nucleus and ultimately results in inflammation. Current treatment strategies for IBD include biologics that specifically bind to a single cytokine or receptor or receptor or other mediators of gastrointestinal inflammation suppressing the specific cytokine signals and limiting inflammation. Given the involvement of multiple cytokines in IBD, a treatment approach that blocks multiple signaling pathways may be effective. To do this, researchers have focused on the intracellular portion of the signaling cascade. A large number of cytokines operate by activating the intracellular JAK-STAT pathway. JAKs reside on the intracellular portion of the receptor. When a cytokine binds to the receptor it activates JAKs, which in turn activate signal transducers and activators of transcription, or STATs. Activated STATs move to the nucleus to regulate gene transcription. There are four members of the JAK family: JAK1, JAK2, JAK3, and TYK2. Different receptors rely on different combinations of JAKs and different JAK combinations activate different types of STATs, resulting in specific patterns of gene regulation and a wide range of immune effects. The role of JAKs in multiple cytokine signaling pathways make them an attractive therapeutic target for IBD. Several different JAK inhibitors have been developed. These inhibitors vary in terms of their selectivity for specific JAKs. For example, tofacitinib is a pan-JAK inhibitor and blocks multiple JAKs. In contrast, filgotinib is a selective JAK inhibitor which specifically inhibits JAK1. These differences in selectivity influence which signaling pathways are affected. Whether this results in different clinical effects is not yet fully known. JAK inhibition has the potential to modulate a range of cytokine-induced proinflammatory pathways implicated in IBD.

Duration: 03:09
Licence: All rights reserved
Original Language: English
Published: 2/2/2023
Diseases and Conditions: Inflammatory Bowel Disease
Format: 3D Animation

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JAK-STAT Inhibition in IBD II

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