Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin

Chemerin is a chemotactic agent that was recently identified as the ligand of ChemR23, a serpentine receptor expressed by activated macrophages and monocyte-derived dendritic cells (DCs). This paper shows that blood plasmacytoid and myeloid DCs express functional ChemR23. Recombinant chemerin induced the transmigration of plasmacytoid and myeloid DCs across an endothelial cell monolayer. In secondary lymphoid organs (lymph nodes and tonsils), ChemR23 is expressed by CD123+ plasmacytoid DCs and by CD1a+ DC-SIGN+ DCs in the interfollicular T cell area. ChemR23+ DCs were also observed in dermis from normal skin, whereas Langerhans cells were negative. Chemerin expression was selectively detected on the luminal side of high endothelial venules in secondary lymphoid organs and in dermal endothelial vessels of lupus erythematosus skin lesions. Chemerin+ endothelial cells were surrounded by ChemR23+ plasmacytoid DCs. Thus, ChemR23 is expressed and functional in plasmacytoid DCs, a property shared only by CXCR4 among chemotactic receptors. This finding, together with the selective expression of the cognate ligand on the luminal side of high endothelial venules and inflamed endothelium, suggests a key role of the ChemR23/chemerin axis in directing plasmacytoid DC trafficking.

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Functions of Dendritic Cells and Its Association with Intestinal Diseases

Cells ◽

10.3390/cells10030583 ◽

2021 ◽

Vol 10 (3) ◽

pp. 583

Author(s):

Ze-Jun Yang ◽

Bo-Ya Wang ◽

Tian-Tian Wang ◽

Fei-Fei Wang ◽

Yue-Xin Guo ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Dendritic Cells ◽

Immune System ◽

Regulatory Mechanism ◽

Intestinal Tumors ◽

Regulatory Relationship ◽

Intestinal Diseases ◽

Inflammatory Bowel ◽

Plasmacytoid Dcs

Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs), serve as the sentinel cells of the immune system and are responsible for presenting antigen information. Moreover, the role of DCs derived from monocytes (moDCs) in the development of inflammation has been emphasized. Several studies have shown that the function of DCs can be influenced by gut microbes including gut bacteria and viruses. Abnormal changes/reactions in intestinal DCs are potentially associated with diseases such as inflammatory bowel disease (IBD) and intestinal tumors, allowing DCs to be a new target for the treatment of these diseases. In this review, we summarized the physiological functions of DCs in the intestinal micro-environment, their regulatory relationship with intestinal microorganisms and their regulatory mechanism in intestinal diseases.

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Essential Role of Canonical NF-κB Activity in the Development of Stromal Cell Subsets in Secondary Lymphoid Organs

The Journal of Immunology ◽

10.4049/jimmunol.1800539 ◽

2018 ◽

Vol 201 (12) ◽

pp. 3580-3586

Author(s):

Dana Bogdanova ◽

Arata Takeuchi ◽

Madoka Ozawa ◽

Yasuhiro Kanda ◽

M. Azizur Rahman ◽

...

Keyword(s):

Stromal Cell ◽

Essential Role ◽

Lymphoid Organs ◽

Secondary Lymphoid Organs

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Immunomodulatory Role of the Antimicrobial LL-37 Peptide in Autoimmune Diseases and Viral Infections

Vaccines ◽

10.3390/vaccines8030517 ◽

2020 ◽

Vol 8 (3) ◽

pp. 517 ◽

Cited By ~ 3

Author(s):

Bapi Pahar ◽

Stefania Madonna ◽

Arpita Das ◽

Cristina Albanesi ◽

Giampiero Girolomoni

Keyword(s):

Lupus Erythematosus ◽

Cytokine Production ◽

Viral Infections ◽

Normal Skin ◽

Epidermal Keratinocytes ◽

New Approach ◽

Virus Dissemination ◽

Monocytes And Macrophages ◽

Progression Of Disease

Antimicrobial peptides (AMPs) are produced by neutrophils, monocytes, and macrophages, as well as epithelial cells, and are an essential component of innate immunity system against infection, including several viral infections. AMPs, in particular the cathelicidin LL-37, also exert numerous immunomodulatory activities by inducing cytokine production and attracting and regulating the activity of immune cells. AMPs are scarcely expressed in normal skin, but their expression increases when skin is injured by external factors, such as trauma, inflammation, or infection. LL-37 complexed to self-DNA acts as autoantigen in psoriasis and lupus erythematosus (LE), where it also induces production of interferon by plasmocytoid dendritic cells and thus initiates a cascade of autocrine and paracrine processes, leading to a disease state. In these disorders, epidermal keratinocytes express high amounts of AMPs, which can lead to uncontrolled inflammation. Similarly, LL-37 had several favorable and unfavorable roles in virus replication and disease pathogenesis. Targeting the antiviral and immunomodulatory functions of LL-37 opens a new approach to limit virus dissemination and the progression of disease.

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[93] INTERFERON-ALPHA TREATMENT IN PATIENTS WITH CHRONIC HCV INFECTION SKEWS HOMING PROPERTIES OF CIRCULATING MYELOID DENDRITIC CELLS TO SECONDARY LYMPHOID ORGANS

Journal of Hepatology ◽

10.1016/s0168-8278(07)61691-2 ◽

2007 ◽

Vol 46 ◽

pp. S42

Author(s):

S. Beckebaum ◽

J. Kang ◽

C.G. Klein ◽

C.E. Broelsch ◽

G. Gerken ◽

...

Keyword(s):

Dendritic Cells ◽

Interferon Alpha ◽

Lymphoid Organs ◽

Hcv Infection ◽

Myeloid Dendritic Cells ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Secondary Lymphoid Organs ◽

Interferon Alpha Treatment

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The role of dectin-1 expressing dendritic cells in the pathogenesis of systemic lupus erythematosus

10.5353/th_b4786999 ◽

2011 ◽

Author(s):

Tung-wing Luk

Keyword(s):

Systemic Lupus Erythematosus ◽

Dendritic Cells ◽

Lupus Erythematosus ◽

Systemic Lupus

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Allogeneic Environment and Tissue Damage Provide Critical Stimuli for Regulatory T Cell Expansion and Survival In Vivo after Hematopoietic Cell Transplantation.

Blood ◽

10.1182/blood.v108.11.1731.1731 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1731-1731

Author(s):

Vu H. Nguyen ◽

Daisy Chang ◽

Robert S. Negrin

Keyword(s):

Bone Marrow ◽

T Cells ◽

Tissue Damage ◽

Hematopoietic Cell Transplantation ◽

Critical Role ◽

Lymphoid Organs ◽

Gamma Chain ◽

Secondary Lymphoid Organs

Abstract CD4+CD25+ regulatory T cells (Treg) mediate alloresponses in murine models of bone marrow transplantation (BMT), leading to protection from graft-versus-host disease (GvHD). However, in vivo migration and tissue localization of Treg during this inflammatory response remain unclear. We previously demonstrated co-localization of Treg with effector T cells (Tcon) with initial expansion in secondary lymphoid organs prior to migration into inflamed tissues in a major MHC-mismatched BMT model. To explore the stimuli for Treg proliferation, we evaluated the role of the allogeneic environment by transferring FVB donor luciferase-expressing (luc+) Treg into lethally-irradiated syngeneic recipients. Unlike the allogeneic irradiated setting where Treg expand in the presence or absence of Tcon, adoptively transferred luc+ Treg were not detected in secondary lymphoid organs of syngeneic lethally-irradiated BMT recipients by in vivo bioluminescence imaging (BLI). Syngeneic luc+ Tcon also had significantly different in vivo dynamics, with a 4 day delay and only moderate expansion in lymph nodes. Proliferation was not detected in the spleen, unlike their allogeneic Tcon counterparts, nor in the bone marrow compartments, as seen in lymphopenic models. To assess whether irradiation induced the observed in vivo dynamics of Treg in the allogeneic setting, we transferred FVB luc+ Treg or luc+ Tcon into unirradiated Balb/c Rag2−/−gamma chain (γC) −/− recipients, which lack T, B, and NK cells. After adoptive transfer into Rag2−/−γC−/− recipients, robust Tcon proliferation was observed in secondary lymphoid organs and the bone marrow compartments; however, Treg expansion was weak, and specific localization to lymphoid or nonlymphoid tissues was not observed. Treg were stimulated to localize to and expand in secondary lymphoid organs by the co-transfer of Tcon in unirradiated Rag2−/− (γC) −/− or by conditioning Rag2−/− (γC) −/− recipients with irradiation. Exogenous IL2 administration two weeks following luc+ Treg transfer into unirradiated Rag2−/− (γC) −/− recipients similarly led to localization and expansion of Treg in secondary lymphoid organs. These studies indicate the critical role of proinflammatory cytokines, such as IL2, generated either by irradiation-induced tissue damage or donor Tcon, in the expansion and localization of Treg. Differences between Tcon and Treg expansion in syngeneic or unconditioned allogeneic Rag2−/− γC−/− hosts suggest an important role of conditioning with irradiation alone or in concert with the allogeneic environment, in providing distinct signals for Tcon versus Treg activation, proliferation, and localization.

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Sulfation-dependent recognition of high endothelial venules (HEV)-ligands by L-selectin and MECA 79, and adhesion-blocking monoclonal antibody.

Journal of Experimental Medicine ◽

10.1084/jem.180.6.2219 ◽

1994 ◽

Vol 180 (6) ◽

pp. 2219-2226 ◽

Cited By ~ 195

Author(s):

S Hemmerich ◽

E C Butcher ◽

S D Rosen

Keyword(s):

Monoclonal Antibody ◽

Lymph Node ◽

Lymph Nodes ◽

Lymphoid Organs ◽

Metabolic Inhibitor ◽

Dependent Manner ◽

Independent Molecule ◽

High Endothelial Venules ◽

Additional Ligand ◽

Secondary Lymphoid Organs

L-selectin is a lectin-like receptor that mediates the attachment of lymphocytes to high endothelial venules (HEV) of lymph nodes during the process of lymphocyte recirculation. Two sulfated, mucin-like glycoproteins known as Sgp50/GlyCAM-1 and Sgp90/CD34 have previously been identified as HEV-associated ligands for L-selectin. These proteins were originally detected with an L-selectin/Ig chimera called LEC-IgG. GlyCAM-1 and CD34 are also recognized by an antiperipheral node addressin (PNAd) mAb called MECA 79, which blocks L-selectin-dependent adhesion and selectively stains lymph node HEV. The present study compares the requirements for the binding of MECA 79 and LEC-IgG to HEV-ligands. Whereas desialylation of GlyCAM-1 and CD34 drastically reduced binding to LEC-IgG, this treatment enhanced the binding of GlyCAM-1 to MECA 79. In contrast, the binding of both MECA 79 and LEC-IgG to GlyCAM-1 and CD34 was greatly decreased when the sulfation of these ligands was reduced with chlorate, a metabolic inhibitor of sulfation. Because MECA 79 stains HEV-like vessels at various sites of inflammation, recognition by L-selectin of ligands outside of secondary lymphoid organs may depend on sulfation. In addition to their reactivity with GlyCAM-1 and CD34, both MECA 79 and LEC-IgG recognize an independent molecule of approximately 200 kD in a sulfate-dependent manner. Thus, this molecule, which we designate Sgp200, is an additional ligand for L-selectin.

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Similar antigen cross-presentation capacity and phagocytic functions in all freshly isolated human lymphoid organ–resident dendritic cells

Journal of Experimental Medicine ◽

10.1084/jem.20121103 ◽

2013 ◽

Vol 210 (5) ◽

pp. 1035-1047 ◽

Cited By ~ 163

Author(s):

Elodie Segura ◽

Mélanie Durand ◽

Sebastian Amigorena

Keyword(s):

Dendritic Cells ◽

Immune Responses ◽

Lymphoid Organ ◽

Lymphoid Organs ◽

Endocytic Pathway ◽

Soluble Antigen ◽

Cross Presentation ◽

Antigen Presenting ◽

Secondary Lymphoid Organs

Dendritic cells (DCs) represent a heterogeneous population of antigen-presenting cells that initiate and orient immune responses in secondary lymphoid organs. In mice, lymphoid organ–resident CD8+ DCs are specialized at cross-presentation and have developed specific adaptations of their endocytic pathway (high pH, low degradation, and high export to the cytosol). In humans, blood BDCA3+ DCs were recently shown to be the homologues of mouse CD8+ DCs. They were also proposed to cross-present antigens more efficiently than other blood DC subsets after in vitro activation, suggesting that in humans cross-presentation is restricted to certain DC subsets. The DCs that cross-present antigen physiologically, however, are the ones present in lymphoid organs. Here, we show that freshly isolated tonsil-resident BDCA1+ DCs, BDCA3+ DCs, and pDCs all cross-present soluble antigen efficiently, as compared to macrophages, in the absence of activation. In addition, BDCA1+ and BDCA3+ DCs display similar phagosomal pH and similar production of reactive oxygen species in their phagosomes. All three DC subsets, in contrast to macrophages, also efficiently export internalized proteins to the cytosol. We conclude that all freshly isolated lymphoid organ–resident human DCs, but not macrophages, display high intrinsic cross-presentation capacity.

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