Introduction
Featuring the presence of endometrial tissue outside the uterine cavity,
endometriosis is a chronic inflammatory disorder resulting in pelvic
pain and infertility [1]. Various
immune cell types including neutrophils, macrophages, natural killer
(NK) cells, dendritic cells, and T lymphocytes play significant roles in
the initiation and progression of endometriosis
[2]. Immune cells secret biochemical
factors that facilitate endometriotic cell division, invasion, as well
as angiogenesis [3]. However, the
exact functions and regulatory mechanisms of these immune cells have not
been thoroughly understood.
Previous findings suggest that imbalanced T cell subsets and/or T cell
dysfunction significantly contribute to the elevation of pathological
cytokines and inflammatory reactions at endometriosis tissues. Cytokines
released by peritoneal T cells are predominantly T helper 2 (Th2)
cytokines in endometriosis tissue [4].
Regulatory T cell deficiency seems to promote local inflammation,
angiogenesis, and facilitate the attachment and growth of endometrial
implants [5]. Recent studies have
revealed the role of T helper 17 (Th17) cells in endometriosis
pathophysiology. Th17 cells are defined by the secretion of IL-17A, a
pro-inflammatory cytokine crucial for the development of inflammatory
and autoimmune diseases. The proportion of Th17 cells in endometriosis
lesions is higher than that in the normal endometrium
[6], and their high proportion in
peritoneal fluid (PF) is related to the severity of endometriosis
[7]. Additionally, the functional
features and underlying regulatory mechanisms of Th17 cells in
endometriosis are yet to be completely understood. It is, therefore,
important to isolate live Th17 cells from blood, lymphoid organs, PF,
and endometriosis lesions to disclose the molecular characteristics
critical to their activities. Unfortunately, previous and current Th17
studies in endometriosis patients rely on intracellular staining of
IL-17A for flow cytometry analysis, making the isolation of live Th17
cells impractical. A novel approach to sort live Th17 cells is in urgent
demand for endometriosis research. Several research groups have used an
array of chemokine receptors to dissect T cell subsets including Th17
cells in other diseases [8-11].
However, whether these receptors apply to Th17 detection in
endometriosis remains untested.
In the present study, we use a set of cell surface markers to detect and
sort live Th17 cells from PF of patients with advanced/severe
endometriosis. We found that CCR4, CCR6, IL-17RE, and CD27 defined live
PF Th17 cells. Moreover, RNA-Seq analysis revealed significant distinct
transcript profiles of PF Th17 subpopulations. Therefore, our data
disclose the heterogeneity of PF Th17 cells in endometriosis.