STAT4 controls GM-CSF production by both Th1 and Th17 cells during EAE

Area of Science:

• Immunology
• Neuroimmunology
• T cell biology

Background:

• Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis.
• Mice lacking signal transducer and activator of transcription 4 (STAT4) are resistant to EAE, unlike those with altered IL-12 or IFNγ.
• STAT4 regulates GM-CSF production by CD4 T cells, a cytokine crucial for EAE induction.

Purpose of the Study:

• To investigate the role of STAT4 in regulating GM-CSF production by CD4 T cells in EAE.
• To determine if STAT4 controls GM-CSF production in both Th1 and Th17 effector CD4 T cell subsets.

Main Methods:

• Utilized the MOG(35-55) peptide immunization model of EAE.
• Employed intracellular cytokine staining and mixed bone marrow chimeric mice to assess CD4 T cell-intrinsic STAT4 function.
• Performed STAT4 chromatin-immunoprecipitation (ChIP-PCR) to examine direct interaction with the Csf2 gene.

Main Results:

• STAT4 was found to control CD4 T cell-intrinsic GM-CSF production in both Th1 and Th17 cells during EAE and in vitro.
• STAT4 directly interacts with the Csf2 locus in activated effector CD4 T cells, confirming modulation of GM-CSF.

Conclusions:

• STAT4 plays a previously unrecognized role in regulating GM-CSF production by both Th1 and Th17 effector CD4 T cells in EAE.
• STAT4's ability to modulate Th17 cell effector profiles redefines its function beyond a Th1-centric factor.