REVIEW ARTICLE: Mechanisms Underlying Recruitment and Accumulation of Decidual NK Cells in Uterus During Pregnancy

Santoni, Angela; Carlino, Claudia; Stabile, Helena; Gismondi, Angela

doi:10.1111/j.1600-0897.2008.00598.x

Cited by 62 publications

(42 citation statements)

References 67 publications

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“…Although expression levels can only give estimates for protein levels, previous work (29) shows relative changes between tumor and metastasis in accordance with the here reported protein levels. Remarkably, in nonmalignant tissue like placenta, these chemokines, CXCL12, CX 3 CL1, and CXCL10 in particular, were shown to mediate recruitment of peripheral NK cells into the decidua (30). Hence, tumor tissue containing high concentrations of these chemokines appears to possess mechanisms that prohibit this chemokine-driven recruitment and other mechanisms than a simple lack of chemokines must be responsible for the exclusion of NK cells from CRC tissue.…”

Section: Discussionmentioning

confidence: 99%

Natural Killer Cells are Scarce in Colorectal Carcinoma Tissue Despite High Levels of Chemokines and Cytokines

Halama

Braun

Kahlert

et al. 2011

Clinical Cancer Research

246

192

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Purpose: Tumor infiltrating T lymphocytes in colorectal cancer (CRC) have prognostic impact, but the role of natural killer (NK) cells in CRC tissue is unclear. The contribution of intratumoral cytokines and chemokines in shaping the composition of the inflammatory lymphocytic infiltrate is also unclear.Experimental Design: In this study, localization and densities of NK and T cells within primary CRC, CRC liver metastases, adenomas, and normal tissues were analyzed on whole tissue sections from 112 patients. In a subset of these patients, the most important 50 cytokines and chemokines were quantified in paired serum, primary CRC and adjacent mucosa samples and in CRC liver metastases and correlated with NK and T-cell infiltration, respectively.Results: The various compartments displayed characteristic differences like significantly higher chemokine concentrations in CRC tissue. Most importantly, despite high local chemokine levels, NK cells were generally scarce within CRC tumor tissues, independent of human leukocyte antigen (HLA) class I expression. Adjacent normal mucosa contained normal levels of NK cells. In contrast, corresponding T-cell numbers varied substantially and were positively correlated with higher chemokine levels.Conclusions: Our findings indicate a distinct regulation of NK cells versus T cells in the CRC tumor microenvironment. NK-cell migration into CRC tumor tissue is obviously impaired early during tumor development by mechanisms that do not affect T-cell infiltration.

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Section: Discussionmentioning

confidence: 99%

Natural Killer Cells are Scarce in Colorectal Carcinoma Tissue Despite High Levels of Chemokines and Cytokines

Halama

Braun

Kahlert

et al. 2011

Clinical Cancer Research

246

192

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“…The hallmark of this decidua during early gestation is the high number of NK cells (50 -70% of leukocytes present locally) that exhibit a unique phenotype and specific functions (4,(7)(8)(9)(10). A large number of differentially expressed genes have been identified in decidual NK cells (dNK) 3 and peripheral blood (PB)-NK (11).…”

mentioning

confidence: 99%

Critical and Differential Roles of NKp46- and NKp30-Activating Receptors Expressed by Uterine NK Cells in Early Pregnancy

Costa

Casemayou

Aguerre-Girr

et al. 2008

The Journal of Immunology

128

150

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In early human pregnancy, uterine decidual NK cells (dNK) are abundant and considered as cytokine producers but poorly cytotoxic despite their cytolytic granule content, suggesting a negative control of this latter effector function. To investigate the basis of this control, we examined the relative contribution to the cytotoxic function of different activating receptors expressed by dNK. Using a multicolor flow cytometry analysis, we found that freshly isolated dNK exhibit a unique repertoire of activating and inhibitory receptors, identical among all the donors tested. We then demonstrated that in fresh dNK, mAb-specific engagement of NKp46-, and to a lesser extent NKG2C-, but not NKp30-activating receptors induced intracellular calcium mobilization, perforin polarization, granule exocytosis and efficient target cell lysis. NKp46-mediated cytotoxicity is coactivated by CD2 but dramatically blocked by NKG2A coengagement, indicating that the dNK cytotoxic potential could be tightly controlled in vivo. We finally found that in dNK, mAb-specific engagement of NKp30, but not NKp46, triggered the production of IFN-γ, TNF-α, MIP-1α, MIP-1β, and GM-CSF proinflammatory molecules. These data demonstrate a differential, controlled role of NKp46- and NKp30-activating receptors expressed by dNK that could be critical for the outcome of pregnancy and the killing of uterine cells infected by pathogens.

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“…As mentioned previously, the combination of IL-15 and TGF-β increases T-cell switching to a T reg phenotype, further contributing to key events that initiate fetal tolerance [13]. Interestingly, the number of T regs and uNK cells present in the uterus are higher relative to the peripheral blood, implicating the intensive role these cell types play in local reproductive immunity [35]. The shift from inflammation to tolerance in the FRT during semen exposure has been likened to the changes that occur in the tumor microenvironment, both of which provide protection from immune clearance and allow cells to proliferate in a similar manner [36].…”

Section: Effects Of Seminal Factors In the Frtmentioning

confidence: 83%

Variability in human semen content and its potential effects in the female reproductive tract

Keogan¹,

Siegert²,

Wigdahl³

et al. 2016

J Reprod Biol Health

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Human semen is a complex medium containing high concentrations of cytokines, chemokines, and growth factors that play key roles in orchestrating immune responses during reproduction. These factors are essential to establishing conditions that facilitate fertilization and embryogenesis through modulation of local immune responses in the female reproductive tract. Typically, semen initiates a biphasic process of inflammation that is gradually resolved, leading to immune cell recruitment pivotal to clearing excess sperm and establishing tolerance of the fetal allograft. However, the identity and concentration of factors found in semenmay be altered in the male reproductive tract as a consequence of sexually transmitted infections and infertility conditions. As a result, imbalances in semen content can skew the secretory response of the cervicovaginal epithelium after deposition during heterosexual intercourse, which may distort local immune activity and lead to embryo rejection or enhanced pathogen transmission. Recognizing the array of factors contained in semen and the degree to which they vary is an essential part of understanding the impact of variations in semen content on reproductive biology and the transmission of sexually transmitted disease pathogens.

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REVIEW ARTICLE: Mechanisms Underlying Recruitment and Accumulation of Decidual NK Cells in Uterus During Pregnancy

Cited by 62 publications

References 67 publications

Natural Killer Cells are Scarce in Colorectal Carcinoma Tissue Despite High Levels of Chemokines and Cytokines

Natural Killer Cells are Scarce in Colorectal Carcinoma Tissue Despite High Levels of Chemokines and Cytokines

Critical and Differential Roles of NKp46- and NKp30-Activating Receptors Expressed by Uterine NK Cells in Early Pregnancy

Variability in human semen content and its potential effects in the female reproductive tract

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