Natalia S. Chaimowitz, Madison R. Smith, Lisa R. Forbes Satter
{"title":"JAK/STAT defects and immune dysregulation, and guiding therapeutic choices","authors":"Natalia S. Chaimowitz, Madison R. Smith, Lisa R. Forbes Satter","doi":"10.1111/imr.13312","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Inborn errors of immunity (IEIs) encompass a diverse spectrum of genetic disorders that disrupt the intricate mechanisms of the immune system, leading to a variety of clinical manifestations. Traditionally associated with an increased susceptibility to recurrent infections, IEIs have unveiled a broader clinical landscape, encompassing immune dysregulation disorders characterized by autoimmunity, severe allergy, lymphoproliferation, and even malignancy. This review delves into the intricate interplay between IEIs and the JAK–STAT signaling pathway, a critical regulator of immune homeostasis. Mutations within this pathway can lead to a wide array of clinical presentations, even within the same gene. This heterogeneity poses a significant challenge, necessitating individually tailored therapeutic approaches to effectively manage the diverse manifestations of these disorders. Additionally, JAK–STAT pathway defects can lead to simultaneous susceptibility to both infection and immune dysregulation. JAK inhibitors, with their ability to suppress JAK–STAT signaling, have emerged as powerful tools in controlling immune dysregulation. However, questions remain regarding the optimal selection and dosing regimens for each specific condition. Hematopoietic stem cell transplantation (HSCT) holds promise as a curative therapy for many JAK–STAT pathway disorders, but this procedure carries significant risks. The use of JAK inhibitors as a bridge to HSCT has been proposed as a potential strategy to mitigate these risks.</p>\n </div>","PeriodicalId":178,"journal":{"name":"Immunological Reviews","volume":"322 1","pages":"311-328"},"PeriodicalIF":7.5000,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunological Reviews","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/imr.13312","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Inborn errors of immunity (IEIs) encompass a diverse spectrum of genetic disorders that disrupt the intricate mechanisms of the immune system, leading to a variety of clinical manifestations. Traditionally associated with an increased susceptibility to recurrent infections, IEIs have unveiled a broader clinical landscape, encompassing immune dysregulation disorders characterized by autoimmunity, severe allergy, lymphoproliferation, and even malignancy. This review delves into the intricate interplay between IEIs and the JAK–STAT signaling pathway, a critical regulator of immune homeostasis. Mutations within this pathway can lead to a wide array of clinical presentations, even within the same gene. This heterogeneity poses a significant challenge, necessitating individually tailored therapeutic approaches to effectively manage the diverse manifestations of these disorders. Additionally, JAK–STAT pathway defects can lead to simultaneous susceptibility to both infection and immune dysregulation. JAK inhibitors, with their ability to suppress JAK–STAT signaling, have emerged as powerful tools in controlling immune dysregulation. However, questions remain regarding the optimal selection and dosing regimens for each specific condition. Hematopoietic stem cell transplantation (HSCT) holds promise as a curative therapy for many JAK–STAT pathway disorders, but this procedure carries significant risks. The use of JAK inhibitors as a bridge to HSCT has been proposed as a potential strategy to mitigate these risks.
期刊介绍:
Immunological Reviews is a specialized journal that focuses on various aspects of immunological research. It encompasses a wide range of topics, such as clinical immunology, experimental immunology, and investigations related to allergy and the immune system.
The journal follows a unique approach where each volume is dedicated solely to a specific area of immunological research. However, collectively, these volumes aim to offer an extensive and up-to-date overview of the latest advancements in basic immunology and their practical implications in clinical settings.