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

Homozygous loss-of-function RORγT variants cause severe T cell deficiencies and susceptibility to mycobacterial and candidiasis infections in humans.

• Why it matters: Understanding genetic causes of immune deficiencies helps improve diagnosis and treatment of infectious diseases caused by mycobacteria and Candida.
• What they did: Researchers identified five new patients from diverse ancestries with RORγT mutations, analyzing their immune cell profiles and infection histories through genetic and immunological assessments.
• The result: Findings show RORγT is crucial for innate-like and adaptive T cell development, and its deficiency leads to vulnerability to mycobacteria and Candida, with most patients remaining stable into early adulthood.