The crossroad between immune dysregulation and multifactorial autoimmunity is furtherly highlighted by reports of increased TCR αβ DNTs in patients with SLE and other autoimmune disorders [25], as well as in rare genetic disorders of immune regulation, such as STAT3 gain of function (STAT3-GoF), CTLA-4 haploinsufficiency (CHAI), and others [16, 26–29]. Here, STAT3 is linked to systemic lupus erythematosus.