Soluble MICA in endometriosis pathophysiology: Impairs NK cell degranulation and effector functions

Maria Lúcia Carnevale Marin, Marici Rached Rached, Sandra Maria Monteiro, Jorge Kalil, Maurício Simões Abrão, Verônica Coelho
American journal of reproductive immunology (New York, N.Y. : 1989) · 2024 · vol. 91(3) , pp. e13830 · doi:10.1111/aji.13830 · PMID:38454570 · W4392593847
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This study found that soluble MICA in endometriosis impairs NK cell degranulation and effector functions, leading to decreased cytotoxicity and IFN-γ production.

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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: CD16+ 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.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Cell Degranulation Cell Degranulation Cell Degranulation Cell Degranulation Disease Progression Disease Progression Disease Progression Disease Progression Female Female Female Female Gene Expression Gene Expression Gene Expression Gene Expression

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