Differentiation of Peripheral Blood Monocytes into Dendritic Cells

O’Neill, David; Bhardwaj, Nina

doi:10.1002/0471142735.im22f04s67

Cited by 33 publications

(32 citation statements)

References 25 publications

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“…B cells were activated by IFN-γ (100 ng/mL; eBioscience) and LPS (60 μg/mL; Sigma) for 3 d, and monocytes were stimulated by IFN-γ (100 ng/mL) and LPS (100 ng/mL) for 3 d. DCs were generated from human blood monocytes (50).…”

Section: Methodsmentioning

confidence: 99%

HHLA2 is a member of the B7 family and inhibits human CD4 and CD8 T-cell function

Zhao

Chinai²,

Buhl

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

178

287

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T-cell costimulation and coinhibition generated by engagement of the B7 family and their receptor CD28 family are of central importance in regulating the T-cell response, making these pathways very attractive therapeutic targets. Here we describe HERV-H LTRassociating protein 2 (HHLA2) as a member of the B7 family that shares 10-18% amino acid identity and 23-33% similarity to other human B7 proteins and phylogenetically forms a subfamily with B7x and B7-H3 within the family. HHLA2 is expressed in humans but not in mice, which is unique within the B7 and CD28 families. HHLA2 protein is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation with LPS and IFN-γ. HHLA2 does not interact with other known members of the CD28 family or the B7 family, but does bind a putative receptor that is constitutively expressed not only on resting and activated CD4 and CD8 T cells but also on antigen-presenting cells. HHLA2 inhibits proliferation of both CD4 and CD8 T cells in the presence of T-cell receptor signaling. In addition, HHLA2 significantly reduces cytokine production by T cells including IFN-γ, TNF-α, IL-5, IL-10, IL-13, IL-17A, and IL-22. Thus, we have identified a unique B7 pathway that is able to inhibit human CD4 and CD8 T-cell proliferation and cytokine production. This unique human T-cell coinhibitory pathway may afford unique strategies for the treatment of human cancers, autoimmune disorders, infection, and transplant rejection and may help to design better vaccines. Interactions between members of the B7 ligand and CD28 receptor families generate positive costimulation and negative coinhibition, which are of central importance in regulating T-cell responses (1-3). B7-1/B7-2/CD28/CTLA-4 is the most extensively characterized of these pathways. Ligands B7-1 (CD80) and B7-2 (CD86) on antigen-presenting cells (APCs) bind to CD28 on naïve T cells and provide a major costimulatory signal to activate naïve T cells. After the initial activation, coinhibitory molecule cytotoxic T lymphocyte antigen-4 (CTLA-4, CD152) is induced on T cells and engages the same B7-1 and B7-2 ligands to restrain T-cell function. In contrast to the costimulatory activity of CD28, the interaction of B7-1 or B7-2 with CTLA-4 is essential for limiting the proliferative response of recently activated T cells to antigen and CD28-mediated costimulation.During the past decade, several new pathways in the B7 and CD28 families have been identified, including B7h/ICOS, PD-L1/PD-L2/PD-1, B7-H3/receptor, and B7x/receptor. B7h (4) (also called ICOS-L, B7RP-1 (5), GL50 (6), B7H2 (7), LCOS (8), and CD275) binds to the inducible costimulator (ICOS, CD278) on activated T cells (9), which induces strong phosphatidylinositol 3-kinase activity (10, 11) and leads to the expression of transcription factors involved in follicular helper CD4 T (Tfh) differentiation (12). Therefore, the B7h/ICOS pathway provides critical T-cell help to B cells. Deficiencies in this pathway result in substantially reduced numbers of mem...

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Section: Methodsmentioning

confidence: 99%

HHLA2 is a member of the B7 family and inhibits human CD4 and CD8 T-cell function

Zhao

Chinai²,

Buhl

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

178

287

View full text Add to dashboard Cite

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“…S2 in the supplemental material). Primary human dendritic cells were generated from bead-isolated monocytes by culture in RPMI medium supplemented with interleukin 4 (IL-4) and granulocytemacrophage colony-stimulating factor (GM-CSF) by following current protocols (22).…”

Section: Methodsmentioning

confidence: 99%

Role of the NK Cell-Activating Receptor CRACC in Periodontitis

et al. 2013

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Periodontitis is a highly prevalent, biofilm-mediated chronic inflammatory disease that results in the loss of the tooth-supporting tissues. It features two major clinical entities: chronic periodontitis, which is more common, and aggressive periodontitis, which usually has an early onset and a rapid progression. Natural killer (NK) cells are a distinct subgroup of lymphocytes that play a major role in the ability of the innate immune system to steer immune responses. NK cells are abundant in periodontitis lesions, and NK cell activation has been causally linked to periodontal tissue destruction. However, the exact mechanisms of their activation and their role in the pathophysiology of periodontitis are elusive. Here, we show that the predominant NK cellactivating molecule in periodontitis is CD2-like receptor activating cytotoxic cells (CRACC). We show that CRACC induction was significantly more pronounced in aggressive than chronic periodontitis and correlated positively with periodontal disease severity, subgingival levels of specific periodontal pathogens, and NK cell activation in vivo. We delineate how Aggregatibacter actinomycetemcomitans, an oral pathogen that is causally associated with aggressive periodontitis, indirectly induces CRACC on NK cells via activation of dendritic cells and subsequent interleukin 12 (IL-12) signaling. In contrast, we demonstrate that fimbriae from Porphyromonas gingivalis, a principal pathogen in chronic periodontitis, actively attenuate CRACC induction on NK cells. Our data suggest an involvement of CRACC-mediated NK cell activation in periodontal tissue destruction and point to a plausible distinction in the pathobiology of aggressive and chronic periodontitis that may help explain the accelerated tissue destruction in aggressive periodontitis.

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“…Buffy coats, purchased from New York Blood Center, served as sources for PBMCs. Human monocyte-derived DCs were differentiated from monocyte fractions of PBMCs as described previously (74). Briefly, monocytes that attached to the tissue culture plates from buffy coats were grown at 37°C on 10-cm 2 plates in 10 ml of culture media containing 300 IU/ml recombinant human IL-4 (Immunex) and 116 IU/ml recombinant human GM-CSF (R&D).…”

Section: Human Monocyte-derived Dcsmentioning

confidence: 99%

LXR promotes the maximal egress of monocyte-derived cells from mouse aortic plaques during atherosclerosis regression

Feig¹,

Pineda-Torra²,

Sanson³

et al. 2010

J. Clin. Invest.

Self Cite

162

161

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We have previously shown that mouse atherosclerosis regression involves monocyte-derived (CD68 + ) cell emigration from plaques and is dependent on the chemokine receptor CCR7. Concurrent with regression, mRNA levels of the gene encoding LXRα are increased in plaque CD68 + cells, suggestive of a functional relationship between LXR and CCR7. To extend these results, atherosclerotic Apoe -/-mice sufficient or deficient in CCR7 were treated with an LXR agonist, resulting in a CCR7-dependent decrease in plaque CD68 + cells. To test the requirement for LXR for CCR7-dependent regression, we transplanted aortic arches from atherosclerotic Apoe -/-mice, or from Apoe -/-mice with BM deficiency of LXRα or LXRβ, into WT recipients. Plaques from both LXRα-and LXRβ-deficient Apoe -/-mice exhibited impaired regression. In addition, the CD68 + cells displayed reduced emigration and CCR7 expression. Using an immature DC line, we found that LXR agonist treatment increased Ccr7 mRNA levels. This increase was blunted when LXRα and LXRβ levels were reduced by siRNAs. Moreover, LXR agonist treatment of primary human immature DCs resulted in functionally significant upregulation of CCR7. We conclude that LXR is required for maximal effects on plaque CD68 + cell expression of CCR7 and monocyte-derived cell egress during atherosclerosis regression in mice.

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Differentiation of Peripheral Blood Monocytes into Dendritic Cells

Cited by 33 publications

References 25 publications

HHLA2 is a member of the B7 family and inhibits human CD4 and CD8 T-cell function

HHLA2 is a member of the B7 family and inhibits human CD4 and CD8 T-cell function

Role of the NK Cell-Activating Receptor CRACC in Periodontitis

LXR promotes the maximal egress of monocyte-derived cells from mouse aortic plaques during atherosclerosis regression

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