Analysis of suppressive regulatory T cells and latent transforming growth factor-β-expressing macrophages in endometriosis peritoneal fluid

Suppressed immune response responsible for endometriosis?

Key Points

Highlight:

• Altered proportions of suppressive regulatory T cells (Tregs) in the peritoneal fluid of women with endometriosis may explain the initiation and promotion of endometriosis in the pelvic cavity.

Importance:

• The different immune tolerance caused by Tregs and transforming growth factor-β (TGF-β) is believed to cause endometriosis. Understanding these immune processes may establish new approaches for endometriosis.

What's done here:

• Analysis of Treg subpopulations and TGF-β activity by examining latency-associated peptide (LAP) on the surfaces of specific immune cells collected from the peripheral blood (PB) and peritoneal fluid (PF).
• PB and PF of patients with and without endometriosis were collected from 28 women with endometriosis and 20 disease-free women.
• Three subpopulations of T lymphocytes and CD11b+ mononuclear cells expressing LAP were analyzed using flow cytometry.

Data:

• PF samples of patients with endometriosis have higher proportions of suppressive Tregs (resting and effector Tregs) than in control women.
• Percentage of CD11b+LAP+ macrophages was significantly lower in PF samples from women with endometriosis than controls.
• No significant changes were observed in the PB samples.

 Limitations:

• This cross-sectional study cannot inform whether the changes in TGF-β, LAP+ macrophages, and suppressive Tregs are the cause or consequence of endometriosis.
• The study has a small sample size and thus may carry intrinsic confounding factors.

Lay Summary

One prominent theory of endometriosis origin is the implantation of steroid hormone-sensitive endometrial cells and tissues on the peritoneal surface during retrograde menstruation and caused an inflammatory response. While women exhibit retrograde menstruation, endometriosis may be affected by women suffering immune dysfunction that interferes with the clearing of such implanted lesions. However, the data supporting the theory is conflicting, and the association between endometriosis and Treg subpopulations has not been well studied.

In this study by Hanada et al., the authors focused on assessing the association of Treg subpopulation with endometriosis and TGF-β which are thought to be involved in the pathology of endometriosis. Transforming growth factor-β (TGF-β) being important because it can inhibit the proliferation of immune cells and cytokine production necessary to mount an immune response. The peritoneal fluid comprised mainly of macrophages and activated TGF-β can be measured by levels of LAP on the macrophage cells which release it. Therefore, this study assesses the immunotolerance in endometriosis by analyzing Treg subpopulations and LAP expression in macrophages from the PF and PB collected from women with endometriosis (28 women) and control subjects (20 women).

The data show that the frequencies of regulatory and effector Tregs in the PF were higher in patients with endometriosis than in controls. Also, the percentage of CD11b+LAP+ macrophages was significantly lower in PF samples from women with endometriosis than controls, which may be related to the increasing concentration of TGF-β in the PF of endometriosis patients. There has been a lack of clinical studies to test the use of molecularly targeted drugs to control endometriosis. Monoclonal antibodies against TGF-β and LAP may be a useful approach and remained to be examined.

In summary, the results from this study may explain the suppressed immune response associated with endometriosis. Future studies in a more significant cohort are needed to elucidate the relevance of relevance of Tregs and LAP-TGF-β further.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29391020