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Dendritic Cells and the Establishment of Fetomaternal Tolerance for Successful Human Pregnancy Cover

Dendritic Cells and the Establishment of Fetomaternal Tolerance for Successful Human Pregnancy

Archivum Immunologiae et Therapiae Experimentalis
Volume 72 (2024): Issue 1 (January 2024)
By:
Open Access
|May 2024

Figures & Tables

Fig 1.

Development of DCs as an independent cell lineage showing transcriptional regulation, expression of prominent surface markers, and their functional characteristics. The illustration shows how common progenitors give rise to distinct fractions of DCs, monocytes, and macrophages. MPPs, which are produced from HSCs, go through stages of differentiation to create lineage-restricted progenitors of lymphocytes and myeloid cells, called CMPs. The CMPs are separated into two subsets such as MDPs and GMPs on the basis of Cbfb and Cebpa expression. Based on GFI1 expression, GMPs are divided into two subsets such as cMoPs and granulocyte progenitors. The cMoPs further give rise to LCs, MoDCs, and macrophages, potentially based on the expression of RUNX3, ID-2, IRF8 and IRF4 and ZEB2 expression, respectively. The specification of cDC1s and pDCs is correlated with a high level of IRF8 expression from MDPs. On the other hand, cDC2s are correlated with a high level of IRF4 expression. cDC1s, type 1 conventional DCs; cDC2s, type 2 conventional DCs; cDCs, conventional DC; cDPs, common dendritic cell progenitors; cMoPs, common monocyte progenitor; CMPs, common myeloid progenitors; DCs, dendritic cells; FLT3L, FAM-like tyrosine kinase 3 ligand; GMP, granulocyte-macrophage progenitor; HSCs, hematopoietic stem cells; IFN-α, interferon-α; IFN-β, interferon-β; IL-6, interleukin-6; LCs, Langerhans cells; MDPs, monocyte and dendritic cell progenitors; MoDCs, monocyte derived dendritic cells; MPPs, multipotent progenitors; pDCs, plasmacytoid DCs; TF, transcription factor.
Development of DCs as an independent cell lineage showing transcriptional regulation, expression of prominent surface markers, and their functional characteristics. The illustration shows how common progenitors give rise to distinct fractions of DCs, monocytes, and macrophages. MPPs, which are produced from HSCs, go through stages of differentiation to create lineage-restricted progenitors of lymphocytes and myeloid cells, called CMPs. The CMPs are separated into two subsets such as MDPs and GMPs on the basis of Cbfb and Cebpa expression. Based on GFI1 expression, GMPs are divided into two subsets such as cMoPs and granulocyte progenitors. The cMoPs further give rise to LCs, MoDCs, and macrophages, potentially based on the expression of RUNX3, ID-2, IRF8 and IRF4 and ZEB2 expression, respectively. The specification of cDC1s and pDCs is correlated with a high level of IRF8 expression from MDPs. On the other hand, cDC2s are correlated with a high level of IRF4 expression. cDC1s, type 1 conventional DCs; cDC2s, type 2 conventional DCs; cDCs, conventional DC; cDPs, common dendritic cell progenitors; cMoPs, common monocyte progenitor; CMPs, common myeloid progenitors; DCs, dendritic cells; FLT3L, FAM-like tyrosine kinase 3 ligand; GMP, granulocyte-macrophage progenitor; HSCs, hematopoietic stem cells; IFN-α, interferon-α; IFN-β, interferon-β; IL-6, interleukin-6; LCs, Langerhans cells; MDPs, monocyte and dendritic cell progenitors; MoDCs, monocyte derived dendritic cells; MPPs, multipotent progenitors; pDCs, plasmacytoid DCs; TF, transcription factor.

Fig 2.

Flowchart illustrating the regulation of immune responses to the conceptus by DCs. During a typical pregnancy, tolerogenic stimuli such as trophoblasts, progesterone, PGE2, vitamin D, and environmental cells (such as NK cells and Mϕs) encourage partial activation of the local DC. As a result, anti-inflammatory cytokines (like IL-10) are produced, which encourages the induction of tolerance at the maternal–fetal interface by activating a number of mechanisms like the production of pregnancy-protective Th2/Th3 cytokines and the development of Treg cells, which improve immune system suppression and thereby support fetal tolerance. DC, dendritic cell; imDCs: immature DCs; MHC-II, major histocompatibility complex class II; NK, natural killer; PGE2, prostaglandin E2; TGF-β, transforming growth factor-β.
Flowchart illustrating the regulation of immune responses to the conceptus by DCs. During a typical pregnancy, tolerogenic stimuli such as trophoblasts, progesterone, PGE2, vitamin D, and environmental cells (such as NK cells and Mϕs) encourage partial activation of the local DC. As a result, anti-inflammatory cytokines (like IL-10) are produced, which encourages the induction of tolerance at the maternal–fetal interface by activating a number of mechanisms like the production of pregnancy-protective Th2/Th3 cytokines and the development of Treg cells, which improve immune system suppression and thereby support fetal tolerance. DC, dendritic cell; imDCs: immature DCs; MHC-II, major histocompatibility complex class II; NK, natural killer; PGE2, prostaglandin E2; TGF-β, transforming growth factor-β.

Supplementary Table 1.

Different human DC phenotypes during pregnancy.
Different human DC phenotypes during pregnancy.

Supplementary Table 2.

Different mouse DC phenotypes during pregnancy.
Different mouse DC phenotypes during pregnancy.

DC subsets and their surface markers, and TFs regulating their differentiation and function

SubsetsSurface markersTF regulating differentiationFunctionReferences
pDCsCD11clow, SIGLECH+, CD135+, CD4hi, MHC-IIlow, LY6C+, B220+, PDCA-1+, DNGR-1low, IRF8hi, and IL3RhiTCF4, BCL11a, RUNX1, SPIB, and IRF-8Mediate antiviral immune response, autoimmune disease, and secrete type-1 interferons (IFN-α, IFN-β) and IL-6Shortman et al. (2013), Poltorak and Schraml (2015), Tian et al. (2017), and Anderson et al. (2021)
cDC1CD11c+, MHC-II+, CD135+, CD24+, ZBTB46+, CD8α±, CD205+, XCR1+, and DNGR-1+ID-2, BATF3, IRF8, and NFIL3Cross-present exogenous antigen to CD8+ CTLsShortman and Naik (2007), Poltorak and Schraml (2015), Pakalniškytė and Schraml (2017), Tian et al. (2017), and Anderson et al. (2021)
cDC2CD11b+, MHC-II+, CD135+, ZBTB46+, CD24±, IRF4hi, and CD8αIRF4, RELB, RBPT, PU.1, NOTCH2, and KLF4Heterogeneous in function (promotes Th17 differentiation in lungs and intestine/Th2 response against viral infections).Shortman and Naik (2007), Poltorak and Schraml (2015), Pakalniškytė and Schraml (2017), Tian et al. (2017), Anderson et al. (2021), and Wei et al. (2021)
MoDCsMS4a3+, CD11chi, CD40low, CD80/86low, and HLA-DR+IRF4Facilitates cDC1 to fight against infections and inflammationDomínguez and Ardavín (2010), Poltorak and Schraml (2015), Tian et al. (2017), Tang-Huau and Segura (2019), and Anderson et al. (2021)
LCsMAFB+, CD1a+, and CD207+RUNX3, ID2, and IRF8Induce humoral immunity and present antigens to T cellsKaplan (2010), Poltorak and Schraml (2015), Collin and Milne (2016), Tian et al. (2017), and Anderson et al. (2021)
mDCsCD83+, CD80hi, CD40hi, and MHC-II+,NDProduce IFN-γ, TNF-γ, and IL-15. Promote low NK cell proliferationPeters et al. (1993), Lutz and Schuler (2002), Jeras et al. (2005), Bachy et al. (2008), and Hopkins and Connolly (2012)
imDCsCD83−, SIGN+, CD209+NDPromote angiogenesis and tolerogenic environment in deciduaGardner and Moffett (2003), Kämmerer et al. (2003), and Kwan et al. (2014)
Circulatory DCsNDNDPresent antigens to T cells and induce humoral responseMerad et al. (2013) and Boltjes and Van Wijk (2014)
Migratory DCsNDNDPresent antigens to T cellsBroggi et al. (2013)
Resident DCsNDNDPromote negative selection of T cells and present antigens to CD4+ T cellsTaglauer et al. (2010) and Zhou and Wu (2017)
Tolerogenic DCsCD80+, and CD86+NDInduce tolerance, Treg differentiation, and reduce T cell proliferationSmits et al. (2005) and Hubo et al. (2013), Domogalla et al. (2017), and Takenaka and Quintana (2017)
Inflammatory DCsHLA-DRhi, CD11chi, BDCA1+, CD1a+, CD14+, CD172a+, MHC-IIhi, LY6C, FCERI, CD64+, CD107b, CD115, F4/80+CCR2, and GM-CSFSecrete IL-12, -23, -1a, and -1b, which in turn induce Th1 and Th2 response; play critical role in microbial infectionsButts et al. (2007), Poltorak and Schraml. (2015), and Balan et al. (2019)

miRNA influencing DCs development

miRNATargetRoleReferences
miRNA-520hABCG2HSCs differentiationLiao et al. (2008)
miRNA-129CAMTA1, EIF2C3HSCs differentiationLiao et al. (2008)
miRNA-125bBMF and KLF13HSCs survival and growthOoi et al. (2010)
miRNA-142FLT3Differentiation, development, maintenance of CD4+ DCsMildner et al. (2013a)
miRNA-146aIRAK1, NFKBpDCs survivalKarrich et al. (2013)
DOI: https://doi.org/10.2478/aite-2024-0010 | Journal eISSN: 1661-4917
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Language: English
Submitted on: Feb 7, 2024
Accepted on: Feb 26, 2024
Published on: May 23, 2024
Published by: Hirszfeld Institute of Immunology and Experimental Therapy
In partnership with: Paradigm Publishing Services
Publication frequency: 1 times per year
Keywords:
Dendritic cells,
Pregnancy,
Endometrium,
Hematopoietic stem cells,
Placenta
Related subjects:
Medicine,
Basic medical science,
Biochemistry,
Immunology,
Clinical medicine,
Clinical medicine, other,
Clinical chemistry

© 2024 Deviyani Mahajan, Tarun Kumar, Prasana Kumar Rath, Anjan Kumar Sahoo, Bidyut Prava Mishra, Sudarshan Kumar, Nihar Ranjan Nayak, Manoj Kumar Jena, published by Hirszfeld Institute of Immunology and Experimental Therapy
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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