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000289649 1001_ $$aMa, Sicong$$b0
000289649 245__ $$aSerine enrichment in tumors promotes regulatory T cell accumulation through sphinganine-mediated regulation of c-Fos.
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000289649 520__ $$aCD4+ regulatory T (Treg) cells accumulate in the tumor microenvironment (TME) and suppress the immune system. Whether and how metabolite availability in the TME influences Treg cell differentiation is not understood. Here, we measured 630 metabolites in the TME and found that serine and palmitic acid, substrates required for the synthesis of sphingolipids, were enriched. A serine-free diet or a deficiency in Sptlc2, the rate-limiting enzyme catalyzing sphingolipid synthesis, suppressed Treg cell accumulation and inhibited tumor growth. Sphinganine, an intermediate metabolite in sphingolipid synthesis, physically interacted with the transcription factor c-Fos. Sphinganine c-Fos interactions enhanced the genome-wide recruitment of c-Fos to regions near the transcription start sites of target genes including Pdcd1 (encoding PD-1), which promoted Pdcd1 transcription and increased inducible Treg cell differentiation in vitro in a PD-1-dependent manner. Thus, Sptlc2-mediated sphingolipid synthesis translates the extracellular information of metabolite availability into nuclear signals for Treg cell differentiation and limits antitumor immunity.
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000289649 7001_ $$0P:(DE-He78)a928ded2085c8911822370cad0b4a728$$aSandhoff, Roger$$b1$$eFirst author$$udkfz
000289649 7001_ $$aLuo, Xiu$$b2
000289649 7001_ $$0P:(DE-He78)8379c86250c50c0537999a6576e18aa7$$aShang, Fuwei$$b3
000289649 7001_ $$aShi, Qiaozhen$$b4
000289649 7001_ $$aLi, Zhaolong$$b5
000289649 7001_ $$aWu, Jingxia$$b6
000289649 7001_ $$aMing, Yanan$$b7
000289649 7001_ $$0P:(DE-He78)16e91871b8403eb9e93080b2ff38c0a2$$aSchwarz, Frank$$b8
000289649 7001_ $$0P:(DE-He78)f05eabc961bc296c088b3510d6429d02$$aMadi, Alaa Abdelghani Mohamed$$b9
000289649 7001_ $$0P:(DE-He78)4e185694e1e726dc738bad0a0c41cdd0$$aWeisshaar, Nina$$b10
000289649 7001_ $$0P:(DE-He78)32b6d84a1ad5f50401b97559993ad65d$$aMieg, Alessa$$b11
000289649 7001_ $$0P:(DE-He78)b099c4255c1bff642f4d338ef157596e$$aHering, Marvin$$b12
000289649 7001_ $$0P:(DE-He78)a97252706aa90b10eb9e489f0018ba96$$aZettl, Ferdinand$$b13
000289649 7001_ $$0P:(DE-He78)2fa1684ee51fe55698bed79b570b8a6c$$aYan, Xin$$b14
000289649 7001_ $$0P:(DE-He78)6c644df06759d9295db52a00eac44c0f$$aMohr, Kerstin$$b15
000289649 7001_ $$0P:(DE-He78)ad4b5f19b891aeb51245ce42ff3d92ff$$aten Bosch, Nora$$b16
000289649 7001_ $$0P:(DE-He78)4cbe3abf3c7df5d7fbac1c945e4c2fce$$aLi, Zhe$$b17
000289649 7001_ $$aPoschet, Gernot$$b18
000289649 7001_ $$0P:(DE-He78)86fa3316b7be0d661065d02b3baec3d6$$aRodewald, Hans-Reimer$$b19
000289649 7001_ $$00000-0002-5971-7909$$aPapavasiliou, Nina$$b20
000289649 7001_ $$aWang, Xi$$b21
000289649 7001_ $$00000-0002-5328-9755$$aGao, Pu$$b22
000289649 7001_ $$0P:(DE-He78)0b7ce76033a6756b91f5bfb12602e20b$$aCui, Guoliang$$b23$$eLast author
000289649 773__ $$0PERI:(DE-600)2862556-0$$a10.1126/sciimmunol.adg8817$$gVol. 9, no. 94, p. eadg8817$$n94$$peadg8817$$tScience immunology$$v9$$x2470-9468$$y2024
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