Abstract
Decidual natural killer cells accumulate at the fetal-maternal interface and play a key role in a successful pregnancy. However, their origin is still unknown. Do they derive from peripheral natural killer cells recruited in decidua or do they represent a distinct population that originates in situ? Here, we identified natural killer precursors in decidua and uterus of pregnant mice. These precursors underwent rapid in situ differentiation and large proportions of proliferating immature natural killer cells were present in decidua and uterus as early as gestation day 4.5. Here, we investigated the origin of decidua- and uterus-natural killer cells by performing transfer experiments of peripheral mature natural killer cells or precursors from EGFP+ mice. Results showed that mature natural killer cells did not migrate into decidua and uterus, while precursors were recruited in these organs and differentiated towards natural killer cells. Moreover, decidua- and uterus-natural killer cells displayed unique phenotypic and functional features. They expressed high levels of the activating Ly49D receptor in spite of their immature phenotype. In addition, decidua- and uterus-natural killer cells were poorly cytolytic and produced low amounts of IFN-γ, while they released factors (GM-CSF, VEGF, IP-10) involved in neo-angiogenesis and tissue remodeling. Our data reveal in situ generation of decidual natural killer cells and provide an important correlation between mouse and human decidual natural killer cells, allowing further studies to be carried out on their role in pregnancy-related diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 448-457 |
| Number of pages | 10 |
| Journal | Haematologica |
| Volume | 99 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 1 2014 |
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ASJC Scopus subject areas
- Hematology
- Medicine(all)
Cite this
In vivo generation of decidual natural killer cells from resident hematopoietic progenitors. / Chiossone, Laura; Vacca, Paola; Orecchia, Paola; Croxatto, Daniele; Damonte, Patrizia; Astigiano, Simonetta; Barbieri, Ottavia; Bottino, Cristina; Moretta, Lorenzo; Mingari, Maria Cristina.
In: Haematologica, Vol. 99, No. 3, 01.03.2014, p. 448-457.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In vivo generation of decidual natural killer cells from resident hematopoietic progenitors
AU - Chiossone, Laura
AU - Vacca, Paola
AU - Orecchia, Paola
AU - Croxatto, Daniele
AU - Damonte, Patrizia
AU - Astigiano, Simonetta
AU - Barbieri, Ottavia
AU - Bottino, Cristina
AU - Moretta, Lorenzo
AU - Mingari, Maria Cristina
PY - 2014/3/1
Y1 - 2014/3/1
N2 - Decidual natural killer cells accumulate at the fetal-maternal interface and play a key role in a successful pregnancy. However, their origin is still unknown. Do they derive from peripheral natural killer cells recruited in decidua or do they represent a distinct population that originates in situ? Here, we identified natural killer precursors in decidua and uterus of pregnant mice. These precursors underwent rapid in situ differentiation and large proportions of proliferating immature natural killer cells were present in decidua and uterus as early as gestation day 4.5. Here, we investigated the origin of decidua- and uterus-natural killer cells by performing transfer experiments of peripheral mature natural killer cells or precursors from EGFP+ mice. Results showed that mature natural killer cells did not migrate into decidua and uterus, while precursors were recruited in these organs and differentiated towards natural killer cells. Moreover, decidua- and uterus-natural killer cells displayed unique phenotypic and functional features. They expressed high levels of the activating Ly49D receptor in spite of their immature phenotype. In addition, decidua- and uterus-natural killer cells were poorly cytolytic and produced low amounts of IFN-γ, while they released factors (GM-CSF, VEGF, IP-10) involved in neo-angiogenesis and tissue remodeling. Our data reveal in situ generation of decidual natural killer cells and provide an important correlation between mouse and human decidual natural killer cells, allowing further studies to be carried out on their role in pregnancy-related diseases.
AB - Decidual natural killer cells accumulate at the fetal-maternal interface and play a key role in a successful pregnancy. However, their origin is still unknown. Do they derive from peripheral natural killer cells recruited in decidua or do they represent a distinct population that originates in situ? Here, we identified natural killer precursors in decidua and uterus of pregnant mice. These precursors underwent rapid in situ differentiation and large proportions of proliferating immature natural killer cells were present in decidua and uterus as early as gestation day 4.5. Here, we investigated the origin of decidua- and uterus-natural killer cells by performing transfer experiments of peripheral mature natural killer cells or precursors from EGFP+ mice. Results showed that mature natural killer cells did not migrate into decidua and uterus, while precursors were recruited in these organs and differentiated towards natural killer cells. Moreover, decidua- and uterus-natural killer cells displayed unique phenotypic and functional features. They expressed high levels of the activating Ly49D receptor in spite of their immature phenotype. In addition, decidua- and uterus-natural killer cells were poorly cytolytic and produced low amounts of IFN-γ, while they released factors (GM-CSF, VEGF, IP-10) involved in neo-angiogenesis and tissue remodeling. Our data reveal in situ generation of decidual natural killer cells and provide an important correlation between mouse and human decidual natural killer cells, allowing further studies to be carried out on their role in pregnancy-related diseases.
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UR - http://www.scopus.com/inward/citedby.url?scp=84895729547&partnerID=8YFLogxK
U2 - 10.3324/haematol.2013.091421
DO - 10.3324/haematol.2013.091421
M3 - Article
C2 - 24179150
AN - SCOPUS:84895729547
VL - 99
SP - 448
EP - 457
JO - Haematologica
JF - Haematologica
SN - 0390-6078
IS - 3
ER -