The Update Immune-Regulatory Role of Pro- and Anti-Inflammatory Cytokines in Recurrent Pregnancy Losses
Recurrent pregnancy losses (RPL) is a common reproductive disorder with various underlying etiologies. In recent years, rapid progress has been made in exploring the immunological mechanisms for RPL. A propensity toward Th2 over Th1 and regulatory T (Treg) over Th17 immune responses may be advantage...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/1/132 |
| _version_ | 1797625707912757248 |
|---|---|
| author | Xiuhua Yang Yingying Tian Linlin Zheng Thanh Luu Joanne Kwak-Kim |
| author_facet | Xiuhua Yang Yingying Tian Linlin Zheng Thanh Luu Joanne Kwak-Kim |
| author_sort | Xiuhua Yang |
| collection | DOAJ |
| description | Recurrent pregnancy losses (RPL) is a common reproductive disorder with various underlying etiologies. In recent years, rapid progress has been made in exploring the immunological mechanisms for RPL. A propensity toward Th2 over Th1 and regulatory T (Treg) over Th17 immune responses may be advantageous for reproductive success. In women with RPL and animals prone to abortion, an inordinate expression of cytokines associated with implantation and early embryo development is present in the endometrium or decidua secreted from immune and non-immune cells. Hence, an adverse cytokine milieu at the maternal-fetal interface assaults immunological tolerance, leading to fetal rejection. Similar to T cells, NK cells can be categorized based on the characteristics of cytokines they secrete. Decidual NK (dNK) cells of RPL patients exhibited an increased NK1/NK2 ratio (IFN-γ/IL-4 producing NK cell ratios), leading to pro-inflammatory cytokine milieu and increased NK cell cytotoxicity. Genetic polymorphism may be the underlying etiologies for Th1 and Th17 propensity since it alters cytokine production. In addition, various hormones participate in cytokine regulations, including progesterone and estrogen, controlling cytokine balance in favor of the Th2 type. Consequently, the intricate regulation of cytokines and hormones may prevent the RPL of immune etiologies. Local or systemic administration of cytokines or their antagonists might help maintain adequate cytokine milieu, favoring Th2 over Th1 response or Treg over Th17 immune response in women with RPL. Herein, we provided an updated comprehensive review regarding the immune-regulatory role of pro- and anti-inflammatory cytokines in RPL. Understanding the roles of cytokines involved in RPL might significantly advance the early diagnosis, monitoring, and treatment of RPL. |
| first_indexed | 2024-03-11T10:00:08Z |
| format | Article |
| id | doaj.art-aaa596d03186439f8373833be914df08 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T10:00:08Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-aaa596d03186439f8373833be914df082023-11-16T15:29:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0124113210.3390/ijms24010132The Update Immune-Regulatory Role of Pro- and Anti-Inflammatory Cytokines in Recurrent Pregnancy LossesXiuhua Yang0Yingying Tian1Linlin Zheng2Thanh Luu3Joanne Kwak-Kim4Department of Obstetrics, The First Hospital of China Medical University, Shenyang 110001, ChinaDepartment of Obstetrics, The First Hospital of China Medical University, Shenyang 110001, ChinaThe First Hospital of China Medical University, Shenyang 110001, ChinaReproductive Medicine and Immunology, Obstetrics and Gynecology, Clinical Sciences Department, Chicago Medical School, Rosalind Franklin University of Medicine and Science, Vernon Hills, IL 60061, USAReproductive Medicine and Immunology, Obstetrics and Gynecology, Clinical Sciences Department, Chicago Medical School, Rosalind Franklin University of Medicine and Science, Vernon Hills, IL 60061, USARecurrent pregnancy losses (RPL) is a common reproductive disorder with various underlying etiologies. In recent years, rapid progress has been made in exploring the immunological mechanisms for RPL. A propensity toward Th2 over Th1 and regulatory T (Treg) over Th17 immune responses may be advantageous for reproductive success. In women with RPL and animals prone to abortion, an inordinate expression of cytokines associated with implantation and early embryo development is present in the endometrium or decidua secreted from immune and non-immune cells. Hence, an adverse cytokine milieu at the maternal-fetal interface assaults immunological tolerance, leading to fetal rejection. Similar to T cells, NK cells can be categorized based on the characteristics of cytokines they secrete. Decidual NK (dNK) cells of RPL patients exhibited an increased NK1/NK2 ratio (IFN-γ/IL-4 producing NK cell ratios), leading to pro-inflammatory cytokine milieu and increased NK cell cytotoxicity. Genetic polymorphism may be the underlying etiologies for Th1 and Th17 propensity since it alters cytokine production. In addition, various hormones participate in cytokine regulations, including progesterone and estrogen, controlling cytokine balance in favor of the Th2 type. Consequently, the intricate regulation of cytokines and hormones may prevent the RPL of immune etiologies. Local or systemic administration of cytokines or their antagonists might help maintain adequate cytokine milieu, favoring Th2 over Th1 response or Treg over Th17 immune response in women with RPL. Herein, we provided an updated comprehensive review regarding the immune-regulatory role of pro- and anti-inflammatory cytokines in RPL. Understanding the roles of cytokines involved in RPL might significantly advance the early diagnosis, monitoring, and treatment of RPL.https://www.mdpi.com/1422-0067/24/1/132recurrent pregnancy lossescytokinepregnancyimmunemiscarriage |
| spellingShingle | Xiuhua Yang Yingying Tian Linlin Zheng Thanh Luu Joanne Kwak-Kim The Update Immune-Regulatory Role of Pro- and Anti-Inflammatory Cytokines in Recurrent Pregnancy Losses International Journal of Molecular Sciences recurrent pregnancy losses cytokine pregnancy immune miscarriage |
| title | The Update Immune-Regulatory Role of Pro- and Anti-Inflammatory Cytokines in Recurrent Pregnancy Losses |
| title_full | The Update Immune-Regulatory Role of Pro- and Anti-Inflammatory Cytokines in Recurrent Pregnancy Losses |
| title_fullStr | The Update Immune-Regulatory Role of Pro- and Anti-Inflammatory Cytokines in Recurrent Pregnancy Losses |
| title_full_unstemmed | The Update Immune-Regulatory Role of Pro- and Anti-Inflammatory Cytokines in Recurrent Pregnancy Losses |
| title_short | The Update Immune-Regulatory Role of Pro- and Anti-Inflammatory Cytokines in Recurrent Pregnancy Losses |
| title_sort | update immune regulatory role of pro and anti inflammatory cytokines in recurrent pregnancy losses |
| topic | recurrent pregnancy losses cytokine pregnancy immune miscarriage |
| url | https://www.mdpi.com/1422-0067/24/1/132 |
| work_keys_str_mv | AT xiuhuayang theupdateimmuneregulatoryroleofproandantiinflammatorycytokinesinrecurrentpregnancylosses AT yingyingtian theupdateimmuneregulatoryroleofproandantiinflammatorycytokinesinrecurrentpregnancylosses AT linlinzheng theupdateimmuneregulatoryroleofproandantiinflammatorycytokinesinrecurrentpregnancylosses AT thanhluu theupdateimmuneregulatoryroleofproandantiinflammatorycytokinesinrecurrentpregnancylosses AT joannekwakkim theupdateimmuneregulatoryroleofproandantiinflammatorycytokinesinrecurrentpregnancylosses AT xiuhuayang updateimmuneregulatoryroleofproandantiinflammatorycytokinesinrecurrentpregnancylosses AT yingyingtian updateimmuneregulatoryroleofproandantiinflammatorycytokinesinrecurrentpregnancylosses AT linlinzheng updateimmuneregulatoryroleofproandantiinflammatorycytokinesinrecurrentpregnancylosses AT thanhluu updateimmuneregulatoryroleofproandantiinflammatorycytokinesinrecurrentpregnancylosses AT joannekwakkim updateimmuneregulatoryroleofproandantiinflammatorycytokinesinrecurrentpregnancylosses |