Immune cells and endometriosis pain

The involvement of natural killer cells in endometriosis patients with pelvic pain

Key Points

Highlight:

• Dr. Hu group found that natural killer (NK) cells play an important role in the pathogenesis of endometriosis, especially for patients with pelvic pain.

Importance:

• Suppressing NK cells may help to reduce the progression of pelvic pain in patients with endometriosis.

Background:

• Immune system involvement is widely accepted for endometriosis pathogenesis.
• Estrogen dysfunction stimulates immune cells in the peritoneal cavity affecting T & B cells, peritoneal macrophages, and inflammatory mediators.
• M2 macrophages play key roles in promoting endometriosis progression.
• NK cells contribute to immunosurveillance via their cell surface activating and inhibitory receptors [such as NKG2-D type II integral membrane protein (NKG2D) and CD16 (FcgRIIIa)].
• Reduced NK activity may ve a consequence of ectopic endometrial growth, but their direct relationship has not been studied. 

Key points:

• A total of forty-two patients participated in this study.
• In the blood samples, the levels of the inflammatory cytokines TNFa, IL-1b, IL-6, and IL-7 were significantly upregulated in patients with pelvic pain.
• The proportion of NK cells in the peripheral blood was significantly higher in patients with endometriosis with pelvic pain compared to those without.
• The proteins SAMD9 and RGL2 were more highly expressed in blood samples from patients with pelvic pain.
• These results suggest that the activated NK cells might have cytotoxic effects on endometrial and stromal cells during endometriosis progression, resulting in pelvic pain

Limitations:

• Detailed mechanistic studies are required to determine the causality between immune response, endometriosis, and pelvic pain.

Lay Summary

Endometriosis is an estrogen-dependent inflammatory disorder in women. This disease leads to dysmenorrhea, pelvic pain, and infertility.

The immune reaction is one of the most widely accepted pathologies of endometriosis. Estrogen dysfunction stimulates immune cells in the peritoneal cavity affecting not only T & B lymphocytes, peritoneal macrophages, but also inflammatory mediators. In a previous study, M2 macrophages have been shown to play key roles in promoting endometriosis progression. Importantly, there is crosstalk among macrophages, natural killer (NK) cells, and T cells in the peritoneal microenvironment. NK cells contribute to immunosurveillance via their cell surface activating and inhibitory receptors, such as NKG2-D type II integral membrane protein (NKG2D) and CD16 (FcgRIIIa). A recent study suggested that reduced NK activity was a consequence of ectopic endometrial growth.

However, it is still not clear if the changed immune response is a consequence of ectopic endometrial growth and the cause of pelvic pain, and infertility in endometriosis or not. Therefore, Dr. Hu group investigated the involvement of immune cells in the pathogenesis of endometriosis progression by analyzing blood samples from patients with stable disease and those with pelvic pain. This paper was recently published in the journal “International Medical Research”.

A total of forty-two patients participated in this study. In the blood samples from those patients, inflammatory cytokines TNFa, IL-1b, IL-6, and IL-7 were evaluated and found to be significantly upregulated in patients with pelvic pain.

Immune cell profiling was also performed. The proportion of NK cells in the peripheral blood was significantly higher in patients with endometriosis with pelvic pain compared with patients without pelvic pain. Also, the proteins SAMD9 and RGL2 were more highly expressed in blood samples from patients with pelvic pain. These results suggest that the activated NK cells might have cytotoxic effects on endometrial and stromal cells during endometriosis progression, resulting in pelvic pain.

In conclusion, NK cells play an important role in the pathogenesis of endometriosis in patients with pelvic pain. Suppressing the cytotoxic activity of NK cells may thus help to reduce the progression of pelvic pain in patients with endometriosis.

Research Source: https://pubmed.ncbi.nlm.nih.gov/32727237/