Immune Dysregulation and Cytokine Circuitry in Genital Endometriosis: Mechanistic Insights and Next-Generation Immunotherapeutic Strategies

Year : 2026 | Volume : 16 | 01 | Page :
    By

    Yadav Laxmi,

  • Shubham Singh,

  • Sanjesh Rathi,

  1. B. Pharm Student, Department of Pharmacy, School of Pharmacy, Rai University, Ahmedabad, Gujarat, India
  2. Assistant Professor, Department of Pharmaceutics, School of Pharmacy, Rai University, Ahmedabad, Gujarat, India
  3. Professor and Principal, Department of Pharmaceutics, School of Pharmacy, Rai University, Ahmedabad, Gujarat, India

Abstract

Genital endometriosis is increasingly recognized as an immune-mediated inflammatory disorder driven by complex interactions between dysregulated immune cells, cytokine hubs, and microbiome-derived modulators. This review introduces a novel “immune–cytokine circuitry” framework that unifies innate and adaptive immune abnormalities with key cytokine loops sustaining chronic inflammation, angiogenesis, neuroinflammation, and immune tolerance. Within this circuitry, macrophage polarization, dendritic cell immaturity, NK-cell anergy, Treg expansion, Th17 amplification, and B-cell–mediated autoimmunity converge to establish a microenvironment that enables ectopic endometrial tissues to persist and evade immune clearance. Central cytokine nodes including IL-6, TNF-α, IL-1β, IL-8, IL-17, IL-10, and TGF-β coordinate inflammatory amplification and fibrotic remodeling, forming biochemical hubs that regulate lesion survival and progression. A key novelty of this review is the identification of actionable immunological nodes within this circuitry, providing mechanistic justification for next-generation therapeutic strategies. These include IL-6/STAT3 and IL-17/IL-23 axis inhibitors, NK-cell checkpoint modulation, BAFF-targeted B-cell therapies, Treg/Th17 rebalancing, macrophage reprogramming, and emerging microbiome-based immune correction approaches. The review further outlines a precision immunotherapy paradigm that integrates immune phenotyping, multiplex cytokine profiling, and multi-omics classification to guide individualized treatment selection. By reframing endometriosis through an integrated immunological and translational lens, this review highlights the limitations of conventional hormonal and surgical interventions and underscores the potential of targeted immunomodulation to achieve durable remission, improve fertility outcomes, and reduce recurrence. The proposed framework provides a foundation for future research and clinical trials aimed at developing mechanism-based, patient-specific therapies for genital endometriosis.

Keywords: Immune dysregulation; cytokine circuitry; genital endometriosis; macrophage polarization; NK-cell dysfunction; Treg–Th17 imbalance; immunotherapy; microbiome–immune crosstalk.

How to cite this article:
Yadav Laxmi, Shubham Singh, Sanjesh Rathi. Immune Dysregulation and Cytokine Circuitry in Genital Endometriosis: Mechanistic Insights and Next-Generation Immunotherapeutic Strategies. Research and Reviews: A Journal of Pharmacology. 2025; 16(01):-.
How to cite this URL:
Yadav Laxmi, Shubham Singh, Sanjesh Rathi. Immune Dysregulation and Cytokine Circuitry in Genital Endometriosis: Mechanistic Insights and Next-Generation Immunotherapeutic Strategies. Research and Reviews: A Journal of Pharmacology. 2025; 16(01):-. Available from: https://journals.stmjournals.com/rrjop/article=2025/view=233060


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Ahead of Print Subscription Review Article
Volume 16
01
Received 05/11/2025
Accepted 13/11/2025
Published 25/11/2025
Publication Time 20 Days
105

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