Uterine natural killer cells and recurrent spontaneous abortion

Fu, Yaoyao; Ren, Chune; Qiao, Pengyun; Meng, Yuguang

doi:10.1111/aji.13433

Cited by 23 publications

(14 citation statements)

References 138 publications

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“…During these events, the maternal immune system must accept the genetically incompatible fetuses to allow trophoblast invasion (89). It is known that pregnancy-related diseases, such as RSA and PE, may be closely related to impaired immune tolerance (90,91). TGF-b1 is an important regulator of immune cell function.…”

Section: Tgf-b1 In Pathological Pregnancymentioning

confidence: 99%

Role of Transforming Growth Factor-β1 in Regulating Fetal-Maternal Immune Tolerance in Normal and Pathological Pregnancy

et al. 2021

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Transforming growth factor-β (TGF-β) is composed of three isoforms, TGF-β1, TGF-β2, and TGF-β3. TGF-β1 is a cytokine with multiple biological functions that has been studied extensively. It plays an important role in regulating the differentiation of immune cells and maintaining immune cell functions and immune homeostasis. Pregnancy is a carefully regulated process. Controlled invasion of trophoblasts, precise coordination of immune cells and cytokines, and crosstalk between trophoblasts and immune cells play vital roles in the establishment and maintenance of normal pregnancy. In this systematic review, we summarize the role of TGF-β1 in regulating fetal-maternal immune tolerance in healthy and pathological pregnancies. During healthy pregnancy, TGF-β1 induces the production of regulatory T cells (Tregs), maintains the immunosuppressive function of Tregs, mediates the balance of M1/M2 macrophages, and regulates the function of NK cells, thus participating in maintaining fetal-maternal immune tolerance. In addition, some studies have shown that TGF-β1 is dysregulated in patients with recurrent spontaneous abortion or preeclampsia. TGF-β1 may play a role in the occurrence and development of these diseases and may be a potential target for the treatment of these diseases.

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Section: Tgf-b1 In Pathological Pregnancymentioning

confidence: 99%

Role of Transforming Growth Factor-β1 in Regulating Fetal-Maternal Immune Tolerance in Normal and Pathological Pregnancy

et al. 2021

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“…Clinical features of GATA2 deficiency may include recurrent infections, atypical mycobacterial infections, warts, pulmonary alveolar proteinosis, or lymphedema. Although not with clear association to vascular dysfunction or immune deficiencies, premature labor and miscarriages have been described in GATA2 deficiency ( 9 , 37 ) and other germline conditions ( 38 – 40 ).…”

Section: A Diagnostic Framework To Evaluate a Suspected Germline Pred...mentioning

confidence: 99%

Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies

Avagyan

Shimamura

2022

Front. Oncol.

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Pediatric myelodysplastic syndromes (MDS) often raise concern for an underlying germline predisposition to hematologic malignancies, referred to as germline predisposition herein. With the availability of genetic testing, it is now clear that syndromic features may be lacking in patients with germline predisposition. Many genetic lesions underlying germline predisposition may also be mutated somatically in de novo MDS and leukemias, making it critical to distinguish their germline origin. The verification of a suspected germline predisposition informs therapeutic considerations, guides monitoring pre- and post-treatment, and allows for family counseling. Presentation of MDS due to germline predisposition is not limited to children and spans a wide age range. In fact, the risk of MDS may increase with age in many germline predisposition conditions and can present in adults who lack classical stigmata in their childhood. Furthermore, germline predisposition associated with DDX41 mutations presents with older adult-onset MDS. Although a higher proportion of pediatric patients with MDS will have a germline predisposition, the greater number of MDS diagnoses in adult patients may result in a larger overall number of those with an underlying germline predisposition. In this review, we present a framework for the evaluation of germline predisposition to MDS across all ages. We discuss characteristics of personal and family history, clinical exam and laboratory findings, and integration of genetic sequencing results to assist in the diagnostic evaluation. We address the implications of a diagnosis of germline predisposition for the individual, for their care after MDS therapy, and for family members. Studies on MDS with germline predisposition have provided unique insights into the pathogenesis of hematologic malignancies and mechanisms of somatic genetic rescue vs. disease progression. Increasing recognition in adult patients will inform medical management and may provide potential opportunities for the prevention or interception of malignancy.

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“…GATA2 patients also have an increased risk of neoplasms other than hematologic, likely caused by impaired immunosurveillance ( 10 ). Miscarriages are frequently reported and are probably due to NK lymphopenia ( 28 , 49 ).…”

Section: Clinical Features: Immunodeficiency Bone Marrow Failure and ...mentioning

confidence: 99%

GATA 2 Deficiency: Focus on Immune System Impairment

et al. 2022

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GATA2 deficiency is a disease with a broad spectrum of clinical presentation, ranging from lymphedema, deafness, pulmonary dysfunction to miscarriage and urogenital anomalies, but it is mainly recognized as an immune system and bone marrow disorder. It is caused by various heterozygous mutations in the GATA2 gene, encoding for a zinc finger transcription factor with a key role for the development and maintenance of a pool of hematopoietic stem cells; notably, most of these mutations arise de novo. Patients carrying a mutated allele usually develop a loss of some cell populations, such as B-cell, dendritic cell, natural killer cell, and monocytes, and are predisposed to disseminated human papilloma virus and mycobacterial infections. Also, these patients have a predisposition to myeloid neoplasms, including myelodysplastic syndromes, myeloproliferative neoplasms, chronic myelomonocytic leukaemia. The age of symptoms onset can vary greatly even also within the same family, ranging from early childhood to late adulthood; incidence increases by age and most frequently clinical presentation is between the second and third decade of life. Currently, haematopoietic stem cell transplantation represents the only curative treatment, restoring both the hematopoietic and immune system function.

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Uterine natural killer cells and recurrent spontaneous abortion

Cited by 23 publications

References 138 publications

Role of Transforming Growth Factor-β1 in Regulating Fetal-Maternal Immune Tolerance in Normal and Pathological Pregnancy

Role of Transforming Growth Factor-β1 in Regulating Fetal-Maternal Immune Tolerance in Normal and Pathological Pregnancy

Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies

GATA 2 Deficiency: Focus on Immune System Impairment

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