Human inherited RORγT deficiency encompasses genetic heterogeneity, T cell deficiency, and clinical homogeneity.

Inherited RORγT deficiency causes near-complete depletion of innate-like adaptive T cells and predisposes patients to mycobacterial disease and CMC across diverse ancestries.

• Why it matters: Understanding genetic causes of immune deficiencies helps improve diagnosis and treatment for patients with recurrent infections and immune dysregulation.
• What they did: Researchers identified five new patients from different ancestries, each homozygous for novel loss-of-function RORC variants, and analyzed their immune cell profiles and clinical outcomes.
• The result: Findings show RORγT is crucial for protective immunity against mycobacteria and Candida, with most patients surviving into childhood despite severe immune cell depletion.