RT Journal Article
SR Electronic
T1 Type-2 CD8+ T lymphocytes responsive to PGD2 and LTE4 in severe eosinophilic asthma
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 247171
DO 10.1101/247171
A1 Bart Hilvering
A1 Timothy SC Hinks
A1 Linda Stöger
A1 Emanuele Marchi
A1 Maryam Salimi
A1 Rahul Shrimanker
A1 Wei Liu
A1 Wentao Chen
A1 Jian Luo
A1 Simei Go
A1 Timothy Powell
A1 Jennifer Cane
A1 Samantha Thulborn
A1 Ayako Kurioka
A1 Tianqi Leng
A1 Jamie Matthews
A1 Clare Connolly
A1 Catherine Borg
A1 Mona Bafadhel
A1 Christian B Willberg
A1 Adaikalavan Ramasamy
A1 Ratko Djukanović
A1 Graham Ogg
A1 Ian D Pavord
A1 Paul Klenerman
A1 Luzheng Xue
YR 2018
UL http://biorxiv.org/content/early/2018/01/12/247171.abstract
AB The functions and in vivo roles of type-2 CD8+ T cells in humans have not been well defined and this cell type has been largely overlooked in models of disease. We investigated this in the context of severe asthma with persistent airway eosinophilia - a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8+CRTH2+ (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D2 (PGD2) and cysteinyl leukotriene E4 (LTE4) are also increased in the airways of the same group of patients. In vitro PGD2 and LTE4 function synergistically to trigger Tc2 cell recruitment and activation in a TCR-independent manner. These lipids regulate diverse genes in Tc2 cells inducing type-2 cytokines and many other pro-inflammatory cytokines and chemokines which could contribute to eosinophilia. These findings are consistent with an important innate-like role for human Tc2 cells in severe eosinophilic asthma and suggest a potential target for therapeutic intervention in this and other diseases.