mRNA and protein sequencing of pathogenic STAT3 gain-of-function CD8 killer T cells

The association between cancer and autoimmune disease is unexplained, exemplified by T-cell large granular lymphocytic leukemia (T-LGL) where gain-of-function (GOF) somatic mutations in STAT3 correlate with co-existing autoimmunity. To resolve whether these mutations are the cause or consequence of CD8 clonal expansions and autoimmunity, Masle-Farquhar et al. analyse patients with germline STAT3 GOF syndrome and mice with the T-LGL mutation STAT3K658N or the most common germline mutation, STAT3T716M. CD8 T cells from humans and mice with germline STAT3 GOF mutations underwent TCR mRNA deep sequencing, single-cell RNA and protein sequencing using 10X and CITE-seq.