Uncovering an unconventional JAK1/2-STAT3 branch in macrophage IFNγ signaling
Botman, M.; Huisman, J. M. A.; Drakaki, A.; Maas, S. L.; Witalisz-Siepracka, A.; Stoiber, D.; van der Vorst, E. P. C.; Siebeler, R.; Hoeksema, M. A.
Show abstract
Interferon-{gamma} (IFN{gamma}) is a key cytokine in immune activation, especially anti-viral responses and driver of macrophage activation. It classically signals via JAK1/2-mediated STAT1 homodimers. Here, we identify an alternative, non-canonical signaling component in which IFN{gamma} simultaneously also activates STAT3. Our results show that IFN{gamma} activates STAT3 rapidly and directly through JAK1 and JAK2. We provide the first evidence that STAT3 can form heterodimers with STAT1 in this context and demonstrate that STAT3 is co-recruited to a subset of IFN{gamma}-induced, STAT1-bound regulatory elements. While IFN{gamma} directly activates STAT3, our results reveal that its contribution to gene regulation is limited, indicating that STAT1 easily substitutes the STAT1-STAT3 heterodimer for STAT1 homodimers when STAT3 is absent. These findings uncover STAT3 as a new unconventional player in macrophage IFN{gamma} signaling, underscoring the complex and context-dependent nature of cytokine signaling networks.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A genome-wide screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation 96%
- Competitive binding of STATs to receptor phospho-Tyr motifs accounts for altered cytokine responses in autoimmune disorders 96%
- Mitochondrial respiration contributes to the interferon gamma response in antigen presenting cells 95%
Similar papers in this journal
- TRIM14 is a key regulator of the type I interferon response during Mycobacterium tuberculosis infection 94%
- An IRF4-MYC-mTORC1 integrated pathway controls cell growth and the proliferative capacity of activated B cells during B cell differentiation in vivo 93%
- NF-κB-Inducing Kinase (NIK) Governs the Mitochondrial Respiratory Capacity, Differentiation, and Inflammatory Status of Innate Immune Cells 93%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Alternate isoforms of IRF7 Differentially Regulate Interferon Expression to Tune Response to Viral Infection 93%
- High throughput CRISPR screening identifies genes involved in macrophage viability and inflammatory pathways 93%
- Mitochondrial cyclophilin D promotes disease tolerance by licensing NK cell development and IL-22 production against influenza virus 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.