GM-CSF Is an Essential Regulator of T Cell Activation Competence in Uterine Dendritic Cells during Early Pregnancy in Mice

Moldenhauer, Lachlan M.; Keenihan, Sarah N. Hudson; Hayball, John D.; Robertson, Sarah A.

doi:10.4049/jimmunol.1001374

Cited by 85 publications

(53 citation statements)

References 70 publications

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“…Null mutation and cytokine add-back experiments in mice show that seminal fluid-induced cytokine synthesis in reproductive tract epithelial cells is the first step in the female response to seminal fluid and occurs upstream of inflammatory leukocyte recruitment (43)(44)(45). The data reported in this study are consistent with seminal plasma-induced cytokines acting to control leukocyte recruitment and activation.…”

Section: Discussionsupporting

confidence: 80%

“…A third and potentially critical function for the macrophages and DCs recruited into the cervical stroma and epithelium after coitus is to activate immune responses to sperm and microbial Ags contained within the ejaculate. The increase in APCs induced by seminal fluid in the human cervix is reminiscent of findings in mice and pigs, where macrophages and DCs expressing MHCII, scavenger receptor, and other activation markers invade the uterine endometrium and en- gulf ejaculate material after mating (4,7,45,57). Studies in mice show that these cells have a key function in cross-presenting seminal fluid Ags to activate cognate T cells (13).…”

Section: Discussionmentioning

confidence: 91%

“…Studies in mice show that these cells have a key function in cross-presenting seminal fluid Ags to activate cognate T cells (13). When seminal fluid recruitment of macrophages and DCs is compromised because of genetic CSF2 deficiency, both the capacity to induce T cell responses to seminal fluid Ags and to regain tract sterility after mating is impaired (45,58).…”

Section: Discussionmentioning

confidence: 99%

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Seminal Fluid Induces Leukocyte Recruitment and Cytokine and Chemokine mRNA Expression in the Human Cervix after Coitus

Sharkey

Tremellen

Jasper

et al. 2012

The Journal of Immunology

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In mice, seminal fluid elicits an inflammation-like response in the female genital tract that activates immune adaptations to advance the likelihood of conception and pregnancy. In this study, we examined whether similar changes in leukocyte and cytokine parameters occur in the human cervix in response to the male partner’s seminal fluid. After a period of abstinence in proven-fertile women, duplicate sets of biopsies were taken from the ectocervix in the periovulatory period and again 48 h later, 12 h after unprotected vaginal coitus, vaginal coitus with use of a condom, or no coitus. A substantial influx of CD45+ cells mainly comprising CD14+ macrophages and CD1a+ dendritic cells expressing CD11a and MHC class II was evident in both the stratified epithelium and deeper stromal tissue after coitus. CD3+CD8+CD45RO+ T cells were also abundant and increased after coitus. Leukocyte recruitment did not occur without coitus or with condom-protected coitus. An accompanying increase in CSF2, IL6, IL8, and IL1A expression was detected by quantitative RT-PCR, and microarray analysis showed genes linked with inflammation, immune response, and related pathways are induced by seminal fluid in cervical tissues. We conclude that seminal fluid introduced at intercourse elicits expression of proinflammatory cytokines and chemokines, and a robust recruitment of macrophages, dendritic cells, and memory T cells. The leukocyte and cytokine environment induced in the cervix by seminal fluid appears competent to initiate adaptations in the female immune response that promote fertility. This response is also relevant to transmission of sexually transmitted pathogens and potentially, susceptibility to cervical metaplasia.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Seminal Fluid Induces Leukocyte Recruitment and Cytokine and Chemokine mRNA Expression in the Human Cervix after Coitus

Sharkey

Tremellen

Jasper

et al. 2012

The Journal of Immunology

Self Cite

297

312

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“…However, the numbers of uterine macrophages are not altered in GM-CSF-deficient mice (Moldenhauer et al, 2010), which contrasts data from M-CSF-deficient mice where uterine macrophages are almost absent (Wiktor-Jedrzejczak and Gordon, 1996).…”

Section: The Influence Of M-csf and Il-10 On Decidual Macrophage Polacontrasting

confidence: 47%

Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

Svensson‐Arvelund¹

2015

Linköping University Medical Dissertations

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A successful pregnancy requires that the maternal immune system adapts to tolerate the semi-allogeneic fetal-placental unit. This adaptation mainly occurs locally, i.e. at the fetal-maternal interface, where fetal-derived tissues come into close contact with maternal cells in the uterine endometrium (called decidua during pregnancy). decidual macrophages preferentially secreted the monocyte-and Treg cell-associated chemokines CCL2 and CCL18, while Th1-, Th2-and Th17-related chemokines were produced at low levels. These results suggest that decidual macrophages contribute to create the unique decidual cell composition and a tolerogenic immune environment that is compatible with fetal development. Further, by comparing decidual macrophages with different in vitro macrophage subsets, we showed that M-CSF and

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“…20,21 Athanassakis et al 22 has been showed that granulocyte-macrophage colony stimulating factor (GM-CSF) was also important in pregnancy. This has been followed by the work of Robertson and her colleagues 23 who have shown GM-CSF is not only important in the female, but its production in sperm can also be necessary. Various other studies have been well documented that cytokines and chemokines play a vital role in human pregnancy.…”

Section: Pregnancy Endocrine-like Peptidesmentioning

confidence: 99%

Future directions of clinical laboratory evaluation of pregnancy

et al. 2014

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In recent years, our understanding of how the immune system interacts with the developing fetus and placenta has greatly expanded. There are many laboratories that provide tests for diagnosis of pregnancy outcome in women who have recurrent pregnancy loss (RPL) or pre-eclampsia. These tests are based on the premise that immune response to the fetus is equivalent to the adaptive immune response to a transplant. New understanding leads to the concept that the activated innate response is vital for pregnancy and this can result in more effective testing and treatment to prevent an abnormal pregnancy in the future. We describe here only three such areas for future testing: one area involves sperm and semen and factors necessary for successful fertilization; another area would determine conditions for production of growth factors necessary for implantation in the uterus; finally, the last area would be to determine conditions necessary for the vascularization of the placenta and growing fetus by activated natural killer (NK) cells (combinations of killer cell immunoglobulin-like receptor (KIR) family genes with HLA-C haplotypes) that lead to capability of secreting angiogenic growth factors. These areas are novel but understanding their role in pregnancy can lead to insight into how to maintain and treat pregnancies with complicating factors. Keywords: male factor; preterm labor; recurrent pregnancy loss; seminal plasma; sperm INTRODUCTIONWhen utilizing clinical immunological testing in recurrent pregnancy loss (RPL) or preterm delivery, it should be considered that the primary function of the immune system in pregnancy is angiogenesis and its secondary function is to function as a system to kill and remove foreign pathogens. Alterations in the immune system can affect angiogenesis or the blood flow, which is necessary to maintain placental growth and thereby may divert the immune system from its non-pregnant primary function. At present, the most commonly performed tests to monitor and treat women with RPL are tests for autoantibodies such as antiphospholipid antibodies, antinuclear antibodies and anti-thyroid antibodies.1-3 In addition, assays for lymphocyte subsets and their functions, determination of HLA histocompatibility genes and genes related to thrombophilic conditions are used by some physicians to aid in treatment. Some physicians test women to determine if their RPL are due to an inappropriate inflammatory immune response, which may be treated by anti-inflammatory drug regimens. Some of the tests that are performed have been a matter of controversy but one might consider that women with histories of RPL should be tested to determine if a reason for the repeated miscarriages can be identified. Finally, women with preterm delivery usually are tested for infections or fetal fibronectin which can be helpful in the treatment. 4 The immune system is an endocrine-like system capable of producing numerous peptide hormones (cytokines and chemokines). These hormones are key in the vascularization necessary for pla...

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GM-CSF Is an Essential Regulator of T Cell Activation Competence in Uterine Dendritic Cells during Early Pregnancy in Mice

Cited by 85 publications

References 70 publications

Seminal Fluid Induces Leukocyte Recruitment and Cytokine and Chemokine mRNA Expression in the Human Cervix after Coitus

Seminal Fluid Induces Leukocyte Recruitment and Cytokine and Chemokine mRNA Expression in the Human Cervix after Coitus

Immune regulation at the fetal‐maternal interface with focus on decidual macrophages

Future directions of clinical laboratory evaluation of pregnancy

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