{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:06:59Z","timestamp":1783919219959,"version":"3.55.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>T-cell fate and function are profoundly shaped by microenvironmental nutrient availability. The branched-chain amino acid, leucine, is essential for T-cell function, with its uptake via the solute carrier family 7-member 5 transporter increasing upon activation. As the enzyme catalyzing the first step of leucine degradation, the cytosolic branched-chain aminotransferase (BCATc) is induced upon T-cell activation and subsequently acts as a negative regulator of T-cell activity. However, a major knowledge gap remains regarding how BCATc modulates T-cell function beyond activation, specifically within differentiated T helper cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Novel T-cell conditional knockout mouse models of BCATc, and its mitochondrial isoenzyme, BCATm, were characterized and used as a source of in vitro or ovalbumin-induced CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell subsets in the presence of the leucine competitive antagonist,\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      -acetyl leucine amide (NALA). The studies were complemented by transcriptomic analysis of human T cells using the genomic platform R2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Loss of BCATc enhanced T\n                      <jats:sub>H<\/jats:sub>\n                      1 phenotype as evidenced by the increased expression of T-bet and interferon-\n                      <jats:italic toggle=\"yes\">\u03b3<\/jats:italic>\n                      . Leucine, but not the BCAT isoenzymes, was critical for T\n                      <jats:sub>H<\/jats:sub>\n                      2 and T\n                      <jats:sub>H<\/jats:sub>\n                      17 function as evidenced by the severe reduction in interleukin [IL]-13 and IL-17 release in the presence of NALA. Lastly, a loss of BCATc, or its mitochondrial isozyme, BCATm, facilitated a shift of regulatory T cells (Tregs) to a T\n                      <jats:sub>H<\/jats:sub>\n                      1-like phenotype as judged by the increased populations of T-bet\n                      <jats:sup>+<\/jats:sup>\n                      Foxp3\n                      <jats:sup>+<\/jats:sup>\n                      Tregs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      BCATc is the dominant BCAT isoenzyme with immunoregulatory function in CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell subsets and targetable potential in T-cell immunity.\n                    <\/jats:p>\n                  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