SATB1 ensures appropriate transcriptional programs within naïve CD8(+) T cells

Special AT‐binding protein 1 (SATB1) is a chromatin‐binding protein that has been shown to be a key regulator of T‐cell development and CD4(+) T‐cell fate decisions and function. The underlying function for SATB1 in peripheral CD8(+) T‐cell differentiation processes is largely unknown. To address this, we examined SATB1‐binding patterns in naïve and effector CD8(+) T cells demonstrating that SATB1 binds to noncoding regulatory elements linked to T‐cell lineage–specific gene programs, particularly in naïve CD8(+) T cells. We then assessed SATB1 function using N‐ethyl‐N‐nitrosourea‐mutant mice that exhibit a point mutation in the SATB1 DNA‐binding domain (termed Satb1(m1Anu/m1Anu)). Satb1(m1Anu/m1Anu) mice exhibit diminished SATB1‐binding, naïve, Satb1(m1Anu/m1Anu) CD8(+) T cells exhibiting transcriptional and phenotypic characteristics reminiscent of effector T cells. Upon activation, the transcriptional signatures of Satb1(m1Anu/m1Anu) and wild‐type effector CD8(+) T cells converged. While there were no overt differences, primary respiratory infection of Satb1(m1Anu/m1Anu) mice with influenza A virus (IAV) resulted in a decreased proportion and number of IAV‐specific CD8(+) effector T cells recruited to the infected lung when compared with wild‐type mice. Together, these data suggest that SATB1 has a major role in an appropriate transcriptional state within naïve CD8(+) T cells and ensures appropriate CD8(+) T‐cell effector gene expression upon activation.