The JAK-STAT signaling pathway responds to a spectrum of over 50 cytokines and growth factors, essential for development, differentiation, and organ function. It also dictates immune cell fate and effector functions. Dysregulation of this pathway, characterized by aberrant JAK-STAT signal transduction, can have far-reaching consequences. It triggers proinflammatory cytokine signaling, disrupting immune homeostasis and fostering the development of autoimmune diseases. Hyperactivation of JAK-STAT3/5 is also a core cancer pathway, dominantly activated and essential for cancer maintenance. Therefore, maintaining proper JAK-STAT function is crucial for systemic immune homeostasis and well-being. Variations within JAK-STAT1/3/5-SOCS genes due to genetic changes can alter the function of critical components, leading to hyperactivation or loss of balance in JAKs and STATs activity. This negatively impacts immune responses and predisposes individuals to autoimmune conditions such as rheumatoid arthritis, inflammatory bowel disease, or inflammatory skin diseases, as well as certain cancers that are either initiated or undergoing progression.
Investigating JAK-STAT1/3/5 genetic variations, such as gain/loss of function mutations or single nucleotide polymorphisms (SNPs), provides key insights into JAK-STAT organ and immune cell functions. We aim to understand their critical roles in biological processes like cell differentiation, immune response, and disease pathogenesis, linking new findings with genetic insights. Researchers have identified how genetic variations within the JAK-STAT genes influence pathway function, presenting clinicians with the dilemma of deciding on the best drug choices or considering alternatives such as bone marrow transplantation to combat diseases. Understanding associations between specific genetic variations and autoimmunity or cancers provides insights into disease mechanisms, revealing aspects of personalized medicine. We investigate JAK-STAT1/3/5 genetic determinants that contribute to disease risk or treatment outcomes, aiming to improve patient-tailored interventions. Currently, we have 13 JAK kinase inhibitors clinically approved to battle such diseases. Sequencing efforts reveal many genetic variations that influence responses differently to drugs targeting JAK-STAT hyperactivation. This affects treatment efficacy and can cause negative side effects, such as immunosuppression associated with the outbreak of silent infections or even neoplasia, which are not yet fully understood. Consequently, deciphering the genetic consequences of JAK-STAT variations holds promise for personalized medicine, enabling tailored treatments aligned with individual genetic makeup, ultimately improving therapy.
We welcome submissions of Original Research, Review, and Perspective/Clinical Trial articles covering the mechanistic and pathogenic effects of JAK-STAT1/3/5 genetic variations for this special edition. Authors should elucidate therapeutic effects through JAK/STAT inhibitors, informing both basic and clinical researchers about the needs of patients carrying these genetic mutations/variations and how to identify their functional consequences. Topics include genetic variation, pathway function with disease association, treatment response, and clinical implications. Key questions involve how specific JAK-STAT1/3/5 genetics influence pathway function, how genetic variations may alter the activity of key signaling molecules, and how they impact downstream responses culminating in autoimmunity or cancer. Disease susceptibility, underlying mechanisms, and potential therapeutic targets can be highlighted. Guiding treatment decisions based on genetics to inform readers about personalized medicine insights can be emphasized. Clinical insights into therapy targeting JAK/STAT should discuss mechanisms and molecular pathways involved in immune function and disease, with evidence from clinical trials as translational assets.
Keywords:
JAK-STAT1/3/5, JAK-STAT inhibitors, Autoimmunity, SNPs or Gain/Loss of Function Mutations, Oncoimmunology, Cancer
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
The JAK-STAT signaling pathway responds to a spectrum of over 50 cytokines and growth factors, essential for development, differentiation, and organ function. It also dictates immune cell fate and effector functions. Dysregulation of this pathway, characterized by aberrant JAK-STAT signal transduction, can have far-reaching consequences. It triggers proinflammatory cytokine signaling, disrupting immune homeostasis and fostering the development of autoimmune diseases. Hyperactivation of JAK-STAT3/5 is also a core cancer pathway, dominantly activated and essential for cancer maintenance. Therefore, maintaining proper JAK-STAT function is crucial for systemic immune homeostasis and well-being. Variations within JAK-STAT1/3/5-SOCS genes due to genetic changes can alter the function of critical components, leading to hyperactivation or loss of balance in JAKs and STATs activity. This negatively impacts immune responses and predisposes individuals to autoimmune conditions such as rheumatoid arthritis, inflammatory bowel disease, or inflammatory skin diseases, as well as certain cancers that are either initiated or undergoing progression.
Investigating JAK-STAT1/3/5 genetic variations, such as gain/loss of function mutations or single nucleotide polymorphisms (SNPs), provides key insights into JAK-STAT organ and immune cell functions. We aim to understand their critical roles in biological processes like cell differentiation, immune response, and disease pathogenesis, linking new findings with genetic insights. Researchers have identified how genetic variations within the JAK-STAT genes influence pathway function, presenting clinicians with the dilemma of deciding on the best drug choices or considering alternatives such as bone marrow transplantation to combat diseases. Understanding associations between specific genetic variations and autoimmunity or cancers provides insights into disease mechanisms, revealing aspects of personalized medicine. We investigate JAK-STAT1/3/5 genetic determinants that contribute to disease risk or treatment outcomes, aiming to improve patient-tailored interventions. Currently, we have 13 JAK kinase inhibitors clinically approved to battle such diseases. Sequencing efforts reveal many genetic variations that influence responses differently to drugs targeting JAK-STAT hyperactivation. This affects treatment efficacy and can cause negative side effects, such as immunosuppression associated with the outbreak of silent infections or even neoplasia, which are not yet fully understood. Consequently, deciphering the genetic consequences of JAK-STAT variations holds promise for personalized medicine, enabling tailored treatments aligned with individual genetic makeup, ultimately improving therapy.
We welcome submissions of Original Research, Review, and Perspective/Clinical Trial articles covering the mechanistic and pathogenic effects of JAK-STAT1/3/5 genetic variations for this special edition. Authors should elucidate therapeutic effects through JAK/STAT inhibitors, informing both basic and clinical researchers about the needs of patients carrying these genetic mutations/variations and how to identify their functional consequences. Topics include genetic variation, pathway function with disease association, treatment response, and clinical implications. Key questions involve how specific JAK-STAT1/3/5 genetics influence pathway function, how genetic variations may alter the activity of key signaling molecules, and how they impact downstream responses culminating in autoimmunity or cancer. Disease susceptibility, underlying mechanisms, and potential therapeutic targets can be highlighted. Guiding treatment decisions based on genetics to inform readers about personalized medicine insights can be emphasized. Clinical insights into therapy targeting JAK/STAT should discuss mechanisms and molecular pathways involved in immune function and disease, with evidence from clinical trials as translational assets.
Keywords:
JAK-STAT1/3/5, JAK-STAT inhibitors, Autoimmunity, SNPs or Gain/Loss of Function Mutations, Oncoimmunology, Cancer
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.