Human Leucocyte Antigen G and Murine Qa-2 Are Critical for Myeloid Derived Suppressor Cell Expansion and Activation and for Successful Pregnancy Outcome
During pregnancy, maternal immune system has to balance tightly between protection against pathogens and tolerance towards a semi-allogeneic organism. Dysfunction of this immune adaptation can lead to severe complications such as pregnancy loss, preeclampsia or fetal growth restriction. In the prese...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.787468/full |
| _version_ | 1798025575281983488 |
|---|---|
| author | Stefanie Dietz Julian Schwarz Ana Velic Irene González-Menéndez Leticia Quintanilla-Martinez Nicolas Casadei Alexander Marmé Christian F. Poets Christian Gille Christian Gille Natascha Köstlin-Gille Natascha Köstlin-Gille |
| author_facet | Stefanie Dietz Julian Schwarz Ana Velic Irene González-Menéndez Leticia Quintanilla-Martinez Nicolas Casadei Alexander Marmé Christian F. Poets Christian Gille Christian Gille Natascha Köstlin-Gille Natascha Köstlin-Gille |
| author_sort | Stefanie Dietz |
| collection | DOAJ |
| description | During pregnancy, maternal immune system has to balance tightly between protection against pathogens and tolerance towards a semi-allogeneic organism. Dysfunction of this immune adaptation can lead to severe complications such as pregnancy loss, preeclampsia or fetal growth restriction. In the present study we analyzed the impact of the murine MHC class Ib molecule Qa-2 on pregnancy outcome in vivo. We demonstrate that lack of Qa-2 led to intrauterine growth restriction and increased abortion rates especially in late pregnancy accompanied by a disturbed trophoblast invasion and altered spiral artery remodeling as well as protein aggregation in trophoblast cells indicating a preeclampsia-like phenotype. Furthermore, lack of Qa-2 caused imbalanced immunological adaptation to pregnancy with altered immune cell and especially T-cell homeostasis, reduced Treg numbers and decreased accumulation and functional activation of myeloid-derived suppressor cells. Lastly, we show that application of sHLA-G reduced abortion rates in Qa-2 deficient mice by inducing MDSC. Our results highlight the importance of an interaction between HLA-G and MDSC for pregnancy success and the therapeutic potential of HLA-G for treatment of immunological pregnancy complications. |
| first_indexed | 2024-04-11T18:21:03Z |
| format | Article |
| id | doaj.art-8cfd1af81a2d4baaa9ee618e44cfae93 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T18:21:03Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8cfd1af81a2d4baaa9ee618e44cfae932022-12-22T04:09:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.787468787468Human Leucocyte Antigen G and Murine Qa-2 Are Critical for Myeloid Derived Suppressor Cell Expansion and Activation and for Successful Pregnancy OutcomeStefanie Dietz0Julian Schwarz1Ana Velic2Irene González-Menéndez3Leticia Quintanilla-Martinez4Nicolas Casadei5Alexander Marmé6Christian F. Poets7Christian Gille8Christian Gille9Natascha Köstlin-Gille10Natascha Köstlin-Gille11Department of Neonatology, Tuebingen University Children’s Hospital, Tuebingen, GermanyDepartment of Neonatology, Tuebingen University Children’s Hospital, Tuebingen, GermanyInterfaculty Institute for Cell Biology, Proteome Center Tuebingen (PCT), University of Tuebingen, Tübingen, GermanyDepartment of Pathology, University of Tuebingen, Tübingen, GermanyDepartment of Pathology, University of Tuebingen, Tübingen, GermanyNext Generation Sequencing (NGS) Competence Center Tuebingen (NCCT), Tuebingen, Germany; Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, GermanyGynecology and Obstetrics Practice, Am Lustnauer Tor, Tuebingen, GermanyDepartment of Neonatology, Tuebingen University Children’s Hospital, Tuebingen, GermanyDepartment of Neonatology, Tuebingen University Children’s Hospital, Tuebingen, GermanyDepartment of Neonatology, Heidelberg University Children’s Hospital, Heidelberg, GermanyDepartment of Neonatology, Tuebingen University Children’s Hospital, Tuebingen, GermanyDepartment of Neonatology, Heidelberg University Children’s Hospital, Heidelberg, GermanyDuring pregnancy, maternal immune system has to balance tightly between protection against pathogens and tolerance towards a semi-allogeneic organism. Dysfunction of this immune adaptation can lead to severe complications such as pregnancy loss, preeclampsia or fetal growth restriction. In the present study we analyzed the impact of the murine MHC class Ib molecule Qa-2 on pregnancy outcome in vivo. We demonstrate that lack of Qa-2 led to intrauterine growth restriction and increased abortion rates especially in late pregnancy accompanied by a disturbed trophoblast invasion and altered spiral artery remodeling as well as protein aggregation in trophoblast cells indicating a preeclampsia-like phenotype. Furthermore, lack of Qa-2 caused imbalanced immunological adaptation to pregnancy with altered immune cell and especially T-cell homeostasis, reduced Treg numbers and decreased accumulation and functional activation of myeloid-derived suppressor cells. Lastly, we show that application of sHLA-G reduced abortion rates in Qa-2 deficient mice by inducing MDSC. Our results highlight the importance of an interaction between HLA-G and MDSC for pregnancy success and the therapeutic potential of HLA-G for treatment of immunological pregnancy complications.https://www.frontiersin.org/articles/10.3389/fimmu.2021.787468/fullHLA-GQa-2pregnancymyeloid-derived suppressor cellsabortionpreeclampsia |
| spellingShingle | Stefanie Dietz Julian Schwarz Ana Velic Irene González-Menéndez Leticia Quintanilla-Martinez Nicolas Casadei Alexander Marmé Christian F. Poets Christian Gille Christian Gille Natascha Köstlin-Gille Natascha Köstlin-Gille Human Leucocyte Antigen G and Murine Qa-2 Are Critical for Myeloid Derived Suppressor Cell Expansion and Activation and for Successful Pregnancy Outcome Frontiers in Immunology HLA-G Qa-2 pregnancy myeloid-derived suppressor cells abortion preeclampsia |
| title | Human Leucocyte Antigen G and Murine Qa-2 Are Critical for Myeloid Derived Suppressor Cell Expansion and Activation and for Successful Pregnancy Outcome |
| title_full | Human Leucocyte Antigen G and Murine Qa-2 Are Critical for Myeloid Derived Suppressor Cell Expansion and Activation and for Successful Pregnancy Outcome |
| title_fullStr | Human Leucocyte Antigen G and Murine Qa-2 Are Critical for Myeloid Derived Suppressor Cell Expansion and Activation and for Successful Pregnancy Outcome |
| title_full_unstemmed | Human Leucocyte Antigen G and Murine Qa-2 Are Critical for Myeloid Derived Suppressor Cell Expansion and Activation and for Successful Pregnancy Outcome |
| title_short | Human Leucocyte Antigen G and Murine Qa-2 Are Critical for Myeloid Derived Suppressor Cell Expansion and Activation and for Successful Pregnancy Outcome |
| title_sort | human leucocyte antigen g and murine qa 2 are critical for myeloid derived suppressor cell expansion and activation and for successful pregnancy outcome |
| topic | HLA-G Qa-2 pregnancy myeloid-derived suppressor cells abortion preeclampsia |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.787468/full |
| work_keys_str_mv | AT stefaniedietz humanleucocyteantigengandmurineqa2arecriticalformyeloidderivedsuppressorcellexpansionandactivationandforsuccessfulpregnancyoutcome AT julianschwarz humanleucocyteantigengandmurineqa2arecriticalformyeloidderivedsuppressorcellexpansionandactivationandforsuccessfulpregnancyoutcome AT anavelic humanleucocyteantigengandmurineqa2arecriticalformyeloidderivedsuppressorcellexpansionandactivationandforsuccessfulpregnancyoutcome AT irenegonzalezmenendez humanleucocyteantigengandmurineqa2arecriticalformyeloidderivedsuppressorcellexpansionandactivationandforsuccessfulpregnancyoutcome AT leticiaquintanillamartinez humanleucocyteantigengandmurineqa2arecriticalformyeloidderivedsuppressorcellexpansionandactivationandforsuccessfulpregnancyoutcome AT nicolascasadei humanleucocyteantigengandmurineqa2arecriticalformyeloidderivedsuppressorcellexpansionandactivationandforsuccessfulpregnancyoutcome AT alexandermarme humanleucocyteantigengandmurineqa2arecriticalformyeloidderivedsuppressorcellexpansionandactivationandforsuccessfulpregnancyoutcome AT christianfpoets humanleucocyteantigengandmurineqa2arecriticalformyeloidderivedsuppressorcellexpansionandactivationandforsuccessfulpregnancyoutcome AT christiangille humanleucocyteantigengandmurineqa2arecriticalformyeloidderivedsuppressorcellexpansionandactivationandforsuccessfulpregnancyoutcome AT christiangille humanleucocyteantigengandmurineqa2arecriticalformyeloidderivedsuppressorcellexpansionandactivationandforsuccessfulpregnancyoutcome AT nataschakostlingille humanleucocyteantigengandmurineqa2arecriticalformyeloidderivedsuppressorcellexpansionandactivationandforsuccessfulpregnancyoutcome AT nataschakostlingille humanleucocyteantigengandmurineqa2arecriticalformyeloidderivedsuppressorcellexpansionandactivationandforsuccessfulpregnancyoutcome |