Tissue Resident Memory γδT Cells in Murine Uterus Expressed High Levels of IL-17 Promoting the Invasion of Trophocytes

Abstract

γδT cells are non-conventional T cells and serve as the bridge for connecting the innate and adaptive immune systems. γδT cells form a substantial population at barrier sites and play an important role in the development of physiology, inflammation, autoimmune diseases and tumors. γδT cells not only distribute in the maternal-fetal interface during pregnancy but also in non-pregnant uterus. However, the phenotypes and functions of γδT cells in uterus were not clear. In the current study, we found that the percentages of γδT cells were significantly higher in uterus than peripheral blood and most of γδT cells in uterus were distributed in endometrium. Further studies indicated that the majority of γδT cells in uterus were memory cells with higher expression of CD44 and CD27 but lower expression of CD62L and CCR7 compared to those in blood. In addition, we found that γδT cells in uterus were tissue resident memory γδT cells expressing CD69, expressed high levels of CCR6, GranzymeB and CD107a. Moreover, γδT cells in uterus were activated and fully expressed transcription factor RORγt. After short time of activation, γδT cells in uterus significantly expressed high levels of IL-17 but not IFN-γ, which promotes the invasion of murine trophocytes. Taken together, our study will lay the foundation for future research on uterine γδT cells in pregnancy and autoimmune disease.

Estrogen enhanced the expression of IL‐17 by tissue‐resident memory γδT cells from uterus via interferon regulatory factor 4

“…Our previous work showed that γδT cells were enriched in uterus and highly expressed IL-17. 20 In the present study, we found that estrogen could increase the production of IL-17 in uterus after stimulation with anti-CD3 in vitro. During polyclonal activation, γδT cells in uterus expressed high levels of IL-17 but the expression of IFN-γ was much scarcer.…”

“…In addition, uterine γδT cells produced high levels of IL-17 that were the main source of IL-17 in uterus to promote the invasion of trophocytes in vitro. 20 Our current study showed that subcutaneous injection of mice with estrogen could recruit γδT cells to uterus by CXCR3-CXCL10 chemokine axis. In addition, we found that estrogen enhanced the production of IL-17 by promoting the expression of transcription factor IRF-4 at mRNA and protein levels but not RORγt and STAT3.…”

“…The procedures for studying cell phenotype, intracellular cytokines, and transcriptional factor expression had been previously described. 20 Generally, the cells were washed and suspended in 100 μl of PBS containing 0.1% BSA and 0.05% sodium azide. For surface staining, the cells were incubated with the respective mAbs at 4°C in the dark for 30 min.…”

Novel insights based on the plasticity of γδ T cells in the tumor microenvironment

“…In the mesenteric lymph nodes of mice infected with Listeria, Vγ4 + and Vγ6 + γδT17 cells can rapidly proliferate in response to that pathogen in a TCR-dependent manner [64]. Similar memory-like γδT17 cell responses have also been observed in mouse models of psoriasis dermatitis and Staphylococcus aureus infection [65]. Of course, this phenomenon may be due to an increased frequency of γδT17 cells, resulting in activity accumulation.…”

Nanoparticle-delivered TLR4 and RIG-I agonists enhance immune response to SARS-CoV-2 subunit vaccine

“…56 Cell populations bearing tissue-resident memory T cell markers (CD69 + CD103 + ) also increased. Because these T cells were CD4 − CD8 − we speculate they could be γδ T cells, a subset of T cells enriched in epithelial and mucosal tissues that are activated in an MHC-independent manner 57,58 . Unexpectedly, in post-booster BAL fluid and sera, antigen-specific IgG and IgA were present following intranasal vaccination with MPLA NPs plus S-S, but not with PUUC NPs or MPLA+PUUC NPs.…”