Transcription factor RORα enforces stability of the Th17 cell effector program by binding to a Rorc cis-regulatory...

Area of Science:

• Immunology
• Molecular Biology
• Cellular Biology

Background:

• T helper 17 (Th17) cells are vital for mucosal immunity but implicated in autoinflammatory diseases.
• Transcriptional regulation sustaining Th17 cells in vivo is not fully understood.
• RORγt is essential for Th17 differentiation, but RORα's role remains unclear.

Purpose of the Study:

• To investigate the distinct role of RORα in Th17 cell function and maintenance in vivo.
• To elucidate the molecular mechanisms underlying RORα's contribution to Th17 responses.

Main Methods:

• Analysis of Th17 cell differentiation and function in RORα-deficient T cell models.
• Assessment of RORγt expression and Th17 cell effector functions.
• Chromatin immunoprecipitation sequencing to identify RORα and RORγt binding sites.

Main Results:

• RORα is dispensable for Th17 cell differentiation but essential for optimal responses in peripheral tissues.
• Absence of RORα leads to decreased RORγt expression and impaired Th17 effector function.
• Cooperative binding of RORα and RORγt to a novel Rorc cis-regulatory element is critical for Th17 lineage maintenance.

Conclusions:

• RORα plays a non-redundant role in Th17 cell lineage maintenance.
• RORα reinforces the RORγt transcriptional program, ensuring sustained Th17 cell function in vivo.