STAT wars: how STATopathies sabotage innate immunity

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway regulates immune and tissue homeostasis.
• STATopathies, caused by mutations in STAT genes, are increasingly recognized monogenic inborn errors of immunity.
• While STATs are studied in adaptive immunity, their role in innate immunity is less understood.

Purpose of the Study:

• To review emerging evidence on the role of STAT proteins in innate immunity within STATopathies.
• To highlight the importance of innate immune mechanisms in host defense, inflammation, and immune regulation in these disorders.
• To integrate recent findings on cell-specific STAT functions and therapeutic advances.

Main Methods:

• Literature review of recent studies on STATopathies and innate immunity.
• Synthesis of evidence on STAT protein functions in innate immune cells (monocytes, macrophages, etc.).
• Analysis of novel insights into aberrant STAT signaling and therapeutic strategies.

Main Results:

• Individual STATs have specific roles in innate immune cells like monocytes, macrophages, and NK cells.
• Disrupted STAT signaling affects interferon response, pathogen sensing, and myeloid cell differentiation.
• Therapeutic advances include JAK inhibitors, cytokine blockade, and gene correction.

Conclusions:

• Innate immune dysregulation is a key factor in STATopathies, expanding diagnostic and therapeutic options.
• Integrating innate immune profiling can improve prognostication and treatment selection.
• Understanding STAT control in myeloid cells enables precision immunomodulation and potential cures.