Interleukin-35 expression in B lymphocytes: A new potential biomarker?

Study reveals altered frequencies of IL-35-producing regulatory B-cells in endometriosis

Key Points

Highlight

• Regulatory B-cells (Bregs) and IL-35 play a crucial role in immune suppression and tolerance to self-antigens.

Importance

• Bregs and IL-35 are essential for the survival of endometriotic cells "outside the uterus".
• Understanding their role in endometriosis can provide insights into disease mechanisms and potential treatment strategies.

What's done here

• The frequency of Breg subpopulations and their production of IL-35 in endometriosis was evaluated.
• Blood samples from women with endometriosis and healthy women were analyzed using flow cytometry.
• The frequency of Breg subpopulations such as "B10 cells, immature B-cells, plasmablasts" and their IL-35 production were examined.

Key results 

• Women with endometriosis had lower frequencies of plasmablasts and B10 cells compared to healthy women.
• Women with endometriosis had a higher proportion of IL-35-producing Bregs within the reduced populations of plasmablasts and B10 cells.
• In women with deep infiltration endometriosis (DIE), higher percentages of IL-35-expressing plasmablasts and B10 cells were observed compared to the control group.
• No significant differences were found in the frequencies and IL-35 expression of Bregs between different endometriosis groups (DIE vs. ovarian endometriosis).
• Regarding endometriosis-related infertility, women with an endometriosis fertility index (EFI) 7-9 had an increased percentage of IL-35-producing immature Bregs compared to women with EFI 1-6.

Lay Summary

Regulatory T-cells (Tregs) and B-cells (Bregs) play a crucial role in establishing tolerance to self-antigens and suppressing immune activity. Therefore, in endometriosis, they are requisite for the endometriotic cells to survive outside the uterus. They suppress immune activity by producing cytokines. A new immunosuppressive cytokine produced by Bregs; Interleukin-35 (IL-35) has been studied.

Slawek et al. from Poland focused on investigating the frequency of different subpopulations of Bregs and their ability to produce IL-35 in women with endometriosis compared to healthy women aiming to understand the involvement of Bregs and IL-35 in endometriosis pathogenesis and their potential as therapeutic targets. The study was published in the March 2023 issue of the American Journal of Reproductive Immunology.

Three Breg subpopulations were selected: B10 cells, immature B-cells, and plasmablasts known for their production of the immunosuppressive cytokine IL-10. Flow cytometry was used to analyze blood samples from endometriosis patients and healthy women, examining the frequency of Bregs and IL-35 production.

The results of the study showed that women with endometriosis had lower frequencies of plasmablasts and B10 cells compared to healthy women. However, when examining the percentage of these cells expressing IL-35, an increase was observed in women with endometriosis. This suggests that in endometriosis patients, there is a higher proportion of IL-35-producing Bregs within the reduced populations of plasmablasts and B10 cells. The frequencies of immature B-cells producing IL-35 did not differ between the two groups. Furthermore, in deep infiltrative endometriosis (DIE) and ovarian endometriosis, higher percentages of IL-35-expressing plasmablasts and B10 cells were observed compared to the control group. There were also differences in terms of the endometriosis fertility index (EFI) and the percentage of IL-35-producing immature Bregs.

The researchers state that alterations in the frequencies and IL-35 expression of specific Breg subpopulations may be associated with endometriosis and its severity. They conclude by saying that the use of IL-35 expression in B lymphocytes as a peripheral marker for endometriosis is possible, although further research is needed to fully understand its implications.

Research Source: https://pubmed.ncbi.nlm.nih.gov/36579639/