<p id="P4">Activated T cells differentiate into functional subsets with distinct metabolic
programs.
Glutaminase (GLS) converts glutamine to glutamate to support the tricarboxylic acid
cycle and redox and epigenetic reactions. Here, we identify a key role for GLS in
T cell activation and specification. Though GLS deficiency diminished initial T cell
activation and proliferation and impaired differentiation of Th17 cells, loss of GLS
also increased Tbet to promote differentiation and effector function of CD4 Th1 and
CD8 CTL cells. This was associated with altered chromatin accessibility and gene expression,
including decreased PIK3IP1 in Th1 cells that sensitized to IL-2-mediated mTORC1 signaling.
<i>In vivo</i>, GLS null T cells failed to drive Th17-inflammatory diseases, and Th1
cells had initially
elevated function but exhausted over time. Transient GLS inhibition, however, led
to increased Th1 and CTL T cell numbers. Glutamine metabolism thus has distinct roles
to promote Th17 but constrain Th1 and CTL effector cell differentiation.
</p><p id="P5">
<div class="figure-container so-text-align-c">
<img alt="" class="figure" src="/document_file/c502c026-b9f5-495c-9933-06f0527032ee/PubMedCentral/image/nihms-1003543-f0001.jpg"/>
</div>
</p><p id="P3">Glutamine metabolism, and its effects on chromatin, promotes Th17 but
constrains Th1
and CTL effector cell differentiation.
</p>