The Uterus Immune Microenvironment Features in Physiological and Pathological Conditions

Tissues are the new frontier of discoveries in reproductive immunology, and the uterus represents a particularly compelling organ for immune research. Immune cells are an integral component of tissue physiology and immunity, and the immune microenvironment of the uterus is central to its dynamic functions, including implantation, pregnancy maintenance, and response to disease. Determining how immune cells inhabit, adapt, and defend the uterus can provide critical insights into tissue physiology and may offer novel therapeutic avenues for treating reproductive pathologies, such as infertility, pregnancy complications, and gynecological cancers.

The uterus is not a passive recipient of immune responses; rather, its immune microenvironment is actively involved in orchestrating the survival, development, and function of a diverse array of immune cells, including innate lymphoid cells (ILCs), macrophages, dendritic cells, natural killer (NK) cells, T cells, and myeloid-derived suppressor cells (MDSCs). These immune cells are not only essential for immune surveillance but also contribute to uterine tissue remodeling, homeostasis, and the complex process of pregnancy. The uterine endometrium, a multicellular tissue, undergoes cyclical remodeling in response to ovarian hormones, undergoing breakdown and regeneration each month. This remodeling includes alterations to the epithelial, stromal, glandular, vascular, and immune cell populations, which must adapt to prepare the uterine lining for blastocyst implantation.

Upon successful implantation, the uterine environment undergoes even more transformative changes. Immune cells participate in key events such as decidualization, trophoblast invasion, spiral artery remodeling, and placenta formation—processes that require precise coordination between immune responses, tissue remodeling, and vascular adaptations. The uterine microenvironment during pregnancy is finely tuned by a network of soluble factors, including hormones, cytokines, growth factors, oxygen, and extracellular matrix proteins, which dynamically regulate immune function and tissue development.

In pathological states, this finely balanced uterine immune environment can be disrupted. Conditions such as endometriosis, recurrent pregnancy loss, preterm birth, and uterine cancers reflect immune dysfunction within the uterine microenvironment. In endometriosis, for example, an imbalance in immune cell responses promotes the establishment and persistence of ectopic endometrial tissue, resulting in chronic inflammation and infertility. Similarly, in uterine malignancies, immune evasion mechanisms foster tumor progression and metastasis. Understanding how immune cells interact with the uterine tissue in both healthy and pathological conditions is crucial for identifying new therapeutic targets and improving outcomes in reproductive health.

The goal of this Research Topic is to advance our understanding of how the uterine microenvironment shapes immune responses in physiological and pathological contexts. By elucidating the mechanisms that regulate immune cell development, function, and interactions within the uterus, this topic aims to foster research that can inform the treatment of common uterine disorders and pregnancy complications.

We invite Original Research articles, Reviews, mini-reviews, perspectives, methods, and case reports, addressing, but not limited to, the following topics:
1. Biology and pathology of the uterine immune microenvironment during pregnancy, with a focus on immune regulation at the maternal-fetal interface, decidualization, and placental development.
2. Biology and pathology of the non-pregnant uterine immune microenvironment, including immune responses during the menstrual cycle, in the context of infections, endometriosis, and gynecological cancers (e.g., endometrial carcinoma).
3. Development and function of uterine immune cells, with an emphasis on immune cell populations in the endometrium and their roles in tissue homeostasis, inflammation, and pregnancy outcomes.
4. Interactions of uterine immune cells with maternal decidual cells, fetal cells (e.g., extravillous trophoblasts), and other components of the uterine environment, including the extracellular matrix and vasculature, in both health and disease.

Please note that we do not accept research that consists solely of bioinformatics analysis of either public databases or author-generated omics data.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Uterine natural killer (NK) cells, Endometriosis-associated immune dysfunction, Uterine cancer immune microenvironment, Cytokine networks in uterine homeostasis, Decidual macrophages, Immune tolerance in pregnancy

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.