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- Title
Soluble MICA in endometriosis pathophysiology: Impairs NK cell degranulation and effector functions.
- Authors
Marin, Maria Lucia Carnevale; Rached, Marici Rached; Monteiro, Sandra Maria; Kalil, Jorge; Abrao, Mauricio Simoes; Coelho, Verônica
- Abstract
Problem: Endometriosis exhibits several immune dysfunctions, including deficient natural killer (NK) cell cytotoxicity. MICA (MHC class I chain‐related molecule A) is induced by biological stress and soluble MICA (sMICA) negatively modulates the expression of the activating receptor, NKG2D, reducing NK cells activities. We investigated the involvement of soluble MICA in NK cell‐deficient activity in endometriosis. Methods of study: sMICA levels (serum and peritoneal fluid—PF) were evaluated by ELISA. Circulating NK cell subsets quantification and its NKG2D receptor expression, NK cell cytotoxicity and CD107a, IFN‐γ and IL‐10 expressions by NK cells stimulated with K562 cells were determined by flow cytometry. Results: We found higher sMICA levels (serum and PF) in endometriosis, especially in advanced and deep endometriosis. Endometriosis presented lower percentages of CD56dimCD16+ cytotoxic cells and impaired NK cell responses upon stimulation, resulting in lower CD107a and IFN‐γ expressions, and deficient NK cell cytotoxicity. NK cell stimulation in the MICA‐blocked condition (mimicking the effect of sMICA) showed decreased cytotoxicity in initial endometriosis stages and the emergence of a negative correlation between CD107a expression and sMICA levels. Conclusions: We suggest that soluble MICA is a potential player in endometriosis pathophysiology with involvement in disease progression and severity, contributing to NK cell impaired IFN‐γ response and degranulation. NK cell compartment exhibits multiple perturbations, including quantitative deficiency and impaired cytotoxicity, contributing to inadequate elimination of ectopic endometrial tissue.
- Subjects
KILLER cells; IMMUNE response; ENDOMETRIOSIS; MICA; ASCITIC fluids
- Publication
American Journal of Reproductive Immunology, 2024, Vol 91, Issue 3, p1
- ISSN
1046-7408
- Publication type
Article
- DOI
10.1111/aji.13830