Genetic regulators and environmental stimuli modulate T-cell activation in autoimmunity and cancer. The enzyme co-factor tetrahydrobiopterin (BH4) is involved in the production of monoamine neurotransmitters, the generation of nitric oxide, and pain1,2. Here we uncover a link between these processes, identifying a fundamental role for BH4 in T-cell biology. We find that genetic inactivation of GTP cyclohydrolase 1 (GCH1, the rate-limiting enzyme in the synthesis of BH4) and inhibition of sepiapterin reductase (SPR, the terminal enzyme in its synthetic pathway) severely impair the proliferation of mature mouse and human T cells. BH4 production in activated T cells is linked to alterations in iron metabolism and mitochondrial bioenergetics. In vivo blockade of BH4 synthesis abrogates T-cell-mediated autoimmunity and allergic inflammation, while enhancing BH4 levels through GCH1 overexpression augments responses by CD4- and CD8-expressing T cells, increasing their antitumour activity in vivo. Administration of BH4 to mice markedly reduces tumour growth and expands the population of intratumoral effector T cells. Kynurenine—a tryptophan metabolite that blocks antitumour immunity—inhibits T-cell proliferation in a manner that can be rescued by BH4. Finally, we report the development of a potent SPR antagonist for possible clinical use. Our data uncover GCH1, SPR and their downstream metabolite BH4 as critical regulators of T-cell biology that can be readily manipulated to either block autoimmunity or enhance anticancer immunity.

N-Acetyl-D-glucosamine (NAG), the monomer of the world's second most abundant biopolymer chitin, has been for the first time converted to its corresponding amide/amino substituted sugar alcohols, smaller C2-4 polyols and N-acetylmonoethanolamine (NMEA), over noble metal catalysts in the presence of hydrogen in water. Four commercialized catalysts were investigated, and Ru/C exhibited the best performance-achieving 8.7% NMEA, 6.1% C4 polyols, and 71.9% C6 polyols (N-containing) under 180°C, 40 bar H 2 , 1 h with 1 mol% loading. Kinetic studies were conducted, which revealed four major reaction pathways that lead to various products. In particular, retro-aldol reaction-hydrogenation was confirmed to be the pathway forming NMEA. The effects of additives (NaOH and WO 3 ) on the reaction were also tested.

This paper describes chitin liquefaction in ethylene glycol (EG) under the catalysis of sulfuric acid for the first time. Up to 75% of chitin was liquefied at 165 °C within 90 min by using 8 wt % of acid (refer to the mass of EG). The major products (30% yield) were identified to be hydroxyethyl-2-amino-2-deoxyhexopyranoside (HADP) and hydroxyethyl-2-acetamido-2-deoxyhexopyranoside (HAADP) by GC-MS and confirmed by NMR. Kinetic studies were conducted based on which a plausible mechanism for product formation was proposed. HADP was dominant during the reaction, whereas HAADP formed fast at an initial stage and then most of it was hydrolyzed to HADP. Unreacted chitin residues with different reaction times were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), and solid state NMR. The FTIR results showed that negligible deacetylation reaction occurred, supporting the assumption that HADP was produced from the hydrolysis of HAADP rather than directly from chitin polymer chains. The XRD analysis revealed the gradual decrease in crystallinity with the increase in reaction time, indicating the damage of the crystalline domain by the liquefaction process. The simple, cheap, and efficient liquefaction of chitin opens up a new route to produce chemicals and materials from waste in the fishing industry.