TY - JOUR
AU - Cai, Yuping
AU - Kim, Daniel J.
AU - Takahashi, Takehiro
AU - Broadhurst, David I.
AU - Yan, Hong
AU - Ma, Shuangge
AU - Rattray, Nicholas J. W.
AU - Casanovas-Massana, Arnau
AU - Israelow, Benjamin
AU - Klein, Jon
AU - Lucas, Carolina
AU - Mao, Tianyang
AU - Moore, Adam J.
AU - Muenker, M. Catherine
AU - Oh, Ji Eun
AU - Silva, Julio
AU - Wong, Patrick
AU - Yale IMPACT Research Team
AU - Ko, Albert I.
AU - Khan, Sajid A.
AU - Iwasaki, Akiko
AU - Johnson, Caroline H.
PY - 2021
DA - July
TI - Kynurenic acid may underlie sex-specific immune responses to COVID-19
JO - Science Signaling
VL - 14
IS - 690
DO - https://doi.org/10.1126/scisignal.abf8483
AB - Coronavirus disease 2019 (COVID-19) has poorer clinical outcomes in males than in females, and immune responses underlie these sex-related differences. Because immune responses are, in part, regulated by metabolites, we examined the serum metabolomes of COVID-19 patients. In male patients, kynurenic acid (KA) and a high KA–to–kynurenine (K) ratio (KA:K) positively correlated with age and with inflammatory cytokines and chemokines and negatively correlated with T cell responses. Males that clinically deteriorated had a higher KA:K than those that stabilized. KA inhibits glutamate release, and glutamate abundance was lower in patients that clinically deteriorated and correlated with immune responses. Analysis of data from the Genotype-Tissue Expression (GTEx) project revealed that the expression of the gene encoding the enzyme that produces KA, kynurenine aminotransferase, correlated with cytokine abundance and activation of immune responses in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes in COVID-19, suggesting a positive feedback between metabolites and immune responses in males.
PB - American Association for the Advancement of Science
UR - https://strathprints.strath.ac.uk/77085/
KW - Coronavirus (COVID-19)
ER