Tolerogenic Dendritic Cells in Autoimmunity and Inflammatory Diseases

Morante-Palacios, Octavio; Fondelli, Federico; Ballestar, Esteban; Martínez-Cáceres, Eva

doi:10.1016/j.it.2020.11.001

Cited by 154 publications

(116 citation statements)

References 121 publications

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…A health-threatening phenomenon in tumor metastasis will be a desired one in the fertilization process. Redirecting the immune response to the tolerogenic pathway involves tolerogenic dendritic cells [ 43 , 44 , 45 ]. This may prevent the attack on the spermatozoa and developing embryo.…”

Section: Discussionmentioning

confidence: 99%

Glycoproteins Presenting Galactose and N-Acetylgalactosamine in Human Seminal Plasma as Potential Players Involved in Immune Modulation in the Fertilization Process

Szczykutowicz

Tkaczuk-Włach

Ferens-Sieczkowska

2021

IJMS

View full text Add to dashboard Cite

In light of recent research, there is increasing evidence showing that extracellular semen components have a significant impact on the immune reaction of the female partner, leading to the tolerogenic response enabling the embryo development and implantation as well as further progress of healthy pregnancy. Seminal plasma glycoproteins are rich in the unique immunomodulatory glycoepitopes that may serve as ligands for endogenous lectins that decorate the surface of immune cells. Such interaction may be involved in modulation of the maternal immune response. Among immunomodulatory glycans, Lewis type antigens have been of interest for at least two decades, while the importance of T/Tn antigens and related structures is still far from understanding. In the current work, we applied two plant lectins capable of distinguishing glycoepitopes with terminal GalNAc and Gal to identify glycoproteins that are their efficient carriers. By means of lectin blotting and lectin affinity chromatography followed by LC-MS, we identified lactotransferrin, prolactin inducible protein as well as fibronectin and semenogelins 1 and 2 as lectin-reactive. Net-O-glycosylation analysis results indicated that the latter three may actually carry T and/or Tn antigens, while in the case of prolactin inducible protein and lactotransferrin LacdiNAc and lactosamine glycoepitopes were more probable. STRING bioinformatics analysis linked the identified glycoproteins in the close network, indicating their involvement in immune (partially innate) processes. Overall, our research revealed potential seminal plasma ligands for endogenous Gal/GalNAc specific lectins with a possible role in modulation of maternal immune response during fertilization.

show abstract

Section: Discussionmentioning

confidence: 99%

Glycoproteins Presenting Galactose and N-Acetylgalactosamine in Human Seminal Plasma as Potential Players Involved in Immune Modulation in the Fertilization Process

Szczykutowicz

Tkaczuk-Włach

Ferens-Sieczkowska

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…In human blood, several DC subtypes have been identified: conventional (c)DCs (cDC1 and cDC2), plasmacytoid (p)DCs and inflammatory (i)DCs [ 4 , 25 ]. DCs recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) via membrane-conjunction pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and c-type lectins [ 4 ]. Activated cDCs secrete IL-12 and tumor necrosis factor (TNF)-α, and prime naive CD4 + and CD8 + T cells.…”

Section: Tolerogenic Dendritic Cells Regulate Peripheral Tolerancementioning

confidence: 99%

“…Recent studies have also shown that immune metabolism and the micro-environment plays a pivotal role in controlling the functionality and properties of tolDCs. Epigenetic alterations for future therapies may provide novel targets to modulate the state of tolDCs [ 4 ]. Therefore, immune cell therapy in immunological diseases demands further investigation in the application of myeloid regulatory cells and their effect in vivo via larger clinical trials [ 32 ].…”

Section: Future Perspectives Of a Myeloid-regulated Tolerogenic Environment In Immunological Therapiesmentioning

confidence: 99%

“…These cells became permanently engrafted, and the resulting chimeric adult mice were able to permanently accept skin grafts or other tissues from a similar donor mouse strain [ 2 ]. Whilst these initial results suggested a potential for therapeutic application for humans [ 3 ], more than 70 years of subsequent research has highlighted many obstacles, including the identification, isolation and characterization of tolerogenic immunological donor cells, and the characterization of the inflammatory, transcriptomic, epigenomic, and metabolic aspects of the recipient’s immunological status or disease [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Regulatory Macrophages and Tolerogenic Dendritic Cells in Myeloid Regulatory Cell-Based Therapies

Suuring

Moreau

2021

IJMS

View full text Add to dashboard Cite

Myeloid regulatory cell-based therapy has been shown to be a promising cell-based medicinal approach in organ transplantation and for the treatment of autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, Crohn’s disease and multiple sclerosis. Dendritic cells (DCs) are the most efficient antigen-presenting cells and can naturally acquire tolerogenic properties through a variety of differentiation signals and stimuli. Several subtypes of DCs have been generated using additional agents, including vitamin D3, rapamycin and dexamethasone, or immunosuppressive cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). These cells have been extensively studied in animals and humans to develop clinical-grade tolerogenic (tol)DCs. Regulatory macrophages (Mregs) are another type of protective myeloid cell that provide a tolerogenic environment, and have mainly been studied within the context of research on organ transplantation. This review aims to thoroughly describe the ex vivo generation of tolDCs and Mregs, their mechanism of action, as well as their therapeutic application and assessment in human clinical trials.

show abstract

“…DCs can acquire tolerogenic functions in vivo and in vitro in response to several stimuli, including interleukin (IL)-10, vitamin D3, rapamycin, and glucocorticoids (GCs) 10 . In particular, DCs differentiated from MOs in vitro with GM-CSF, IL-4, and GCs can suppress T cell proliferation in vitro, and display a high level of production of IL-10 and low levels of TNFα and IL-12p70 11,12 .…”

Section: Introductionmentioning

confidence: 99%

MAFB surrogates the glucocorticoid receptor ability to induce tolerogenesis in dendritic cells

Morante-Palacios

Ciudad

Micheroli

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Glucocorticoids (GCs) exert potent anti-inflammatory effects in immune cells through the glucocorticoid receptor (GR). Dendritic cells (DCs), central actors for coordinating immune responses, acquire tolerogenic properties in response to GCs. Tolerogenic DCs (tolDCs) have emerged as a potential treatment for various inflammatory diseases. To date, the underlying cell type-specific regulatory mechanisms orchestrating GC-mediated acquisition of immunosuppressive properties remain poorly understood. In this study, we investigated the transcriptomic and epigenomic remodeling associated with differentiation to DCs in the presence of GCs. Our analysis demonstrates a major role of MAFB in this process, in synergy with GR. GR and MAFB both interact with methylcytosine dioxygenase TET2 and bind to genomic loci that undergo specific demethylation in tolDCs. We also show that the role of MAFB is more extensive, binding to thousands of genomic loci in tolDCs. Finally, MAFB knockdown erases the tolerogenic properties of tolDCs and reverts the specific DNA demethylation and gene upregulation. The preeminent role of MAFB is also demonstrated in vivo for myeloid cells from synovium in rheumatoid arthritis following GC treatment. Our results imply that, once directly activated by GR, MAFB takes over the main roles to orchestrate the epigenomic and transcriptomic remodeling that define the tolerogenic phenotype.

show abstract

Tolerogenic Dendritic Cells in Autoimmunity and Inflammatory Diseases

Cited by 154 publications

References 121 publications

Glycoproteins Presenting Galactose and N-Acetylgalactosamine in Human Seminal Plasma as Potential Players Involved in Immune Modulation in the Fertilization Process

Glycoproteins Presenting Galactose and N-Acetylgalactosamine in Human Seminal Plasma as Potential Players Involved in Immune Modulation in the Fertilization Process

Regulatory Macrophages and Tolerogenic Dendritic Cells in Myeloid Regulatory Cell-Based Therapies

MAFB surrogates the glucocorticoid receptor ability to induce tolerogenesis in dendritic cells

Contact Info

Product

Resources

About