Endometriosis is caused by the presence of endometrial tissue outside the uterine cavity (Chapron et al., 2019). The immune system is crucial for the pathophysiology of endometriosis (Vallve-Juanico et al., 2019). Through secreting pro-inflammatory mediators or direct contact, immune cells support the growth and invasion of endometriotic cells to exacerbate endometriosis (Izumi et al., 2018). Of note, effector T helper (Th) cells contribute to the development of endometriosis. Th cells are divided into Th1, Th2, and Th17 subsets based on their cytokine profiles and unique transcription factor expression (Saravia et al., 2019). Under the instructions of antigen presentation cells and interleukin-12 (IL-12), Th1 cells are differentiated from naïve CD4+ T cells and produce interferon-gamma (IFN-γ). Th2 cells are differentiated under the influence of interleukin-4 (IL-4) and express IL-4, interleukin-5 (IL-5), and interleukin-13 (IL-13). Th17 cells, which produce IL-17 and IL-22, are differentiated by interleukin-6 (IL-6), transforming growth factor-beta (TGF-β), interleukin-21 (IL-21), and interleukin-23 (IL-23) (Saravia et al., 2019). Th1 cells play a significant role in endometriosis development (Takamura et al., 2015, Matteo et al., 2017, Khaleque et al., 2022). In endometriotic tissues, Th17 cells are increased and correlate to endometriosis severity (Takamura et al., 2015, Gogacz et al., 2016). Therefore, Th cells could be targets of endometriosis treatment.

Another Th subset, featuring substantial production of granulocyte macrophage-colony-stimulating factor (GM-CSF) and extremely low expression of IFN-γ, IL-17, T-box expressed in T cells (T-bet), GATA binding protein 3 (GATA3), retinoic acid-related orphan receptor gamma t (RORγt), and forkhead box P3 (Foxp3), was found and termed ThGM cells a decade ago (Zhang et al., 2013, Noster et al., 2014). ThGM cells also produce interleukin-2 (IL-2), TNF-α, interleukin-3 (IL-3), and CC chemokine ligand 20 (CCL20) (Rasouli et al., 2020). ThGM cells promote the immune responses of Th1 and Th17 cells (Zhang et al., 2013). Interleukin-7 (IL-7) and IL-1-beta (IL-1β) are essential for ThGM cell differentiation (Sheng et al., 2014, Rasouli et al., 2022). IL-12 induces the polarization of ThGM cells towards Th1 cells (Noster et al., 2014, Rasouli et al., 2020). Importantly, CC chemokine receptors (CCR) and C-X-C motif chemokine receptors (CXCR) can mark different Th subsets. The phenotype of ThGM cells is CCR10+CCR4+CXCR3−CCR6−, making them distinguishable from Th1 cells expressing CCR5 and CXCR3, Th2 cells expressing CCR3 and CCR8, and Th17 cells expressing CCR4 and CCR6 (Stadhouders et al., 2018, Miyagawa and Asada, 2021, Noster et al., 2014). However, the role of ThGM cells in endometriosis progression is completely unknown. In this study, we uncovered the potential role of ThGM cells in endometriosis development.