Running title: IL-17RE marks Th17 heterogeneity in
endometriosis
Abstract: Endometriosis is a chronic inflammatory disorder
resulting in pelvic pain and infertility. The role of T helper 17 (Th17)
cells in endometriosis remains elusive. In this study, through detecting
CXCR3, CCR4, CCR10, CCR6, interleukin-17 Receptor E (IL-17RE), and CD27,
live RORγt-and-IL-17A-expressing Th17 cells were distinguished and
sorted from peritoneal fluid (PF) of patients with stage III and IV
endometriosis. Furthermore, we found that IL-17RE and CD27 were the
labels of heterogeneous PF Th17 subsets, i.e. IL-17RE-CD27- subset,
IL-17RE+CD27- subset, and IL-17RE+CD27+ subset. The former two subsets
expressed higher IL-17A, GM-CSF, and IL-22 and were more proliferative
than the latter subset. RNA-Seq analysis on IL-17RE+ Th17 subset and
IL-17RE- Th17 subset revealed up-regulation of genes involved in
oxidative phosphorylation and electron transport chain in IL-17RE+ Th17
subset relative to IL-17RE- Th17 subset. Consistently, the IL-17RE+ Th17
subset produced more adenosine triphosphate (ATP) and reactive oxygen
species (ROS) than IL-17RE- Th17 subset. In conclusion, this study
provides a novel method to detect and isolate live PF Th17 cells from
endometriosis patients and unveils the functional and metabolic
heterogeneity of PF Th17 subsets. Therefore, it sheds light on the
elucidation of molecular mechanisms that modulate the function of
pathological Th17 cells in endometriosis.
Keywords:Endometriosis,
T helper 17 (Th17)
cells,
Interleukin 17 Receptor E, CD27, Oxidative phosphorylation,
Electron
transport chain.