Expression and Functional Role of HLA-G in Immune Cells from Patients with Systemic Lupus Erythematosus

Monsiváis‐Urenda, Adriana; Baranda, Lourdes; Álvarez-Quiroga, Crisol; Abud-Mendoza, Carlos; González‐Amaro, Roberto

doi:10.1007/s10875-010-9496-0

Cited by 19 publications

(10 citation statements)

References 50 publications

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“…Our results are similar to those of another study showing decreased expression of HLA-G, a non-classical class I HLA molecule with an important role in regulating the immune response, on macrophages/mature dendritic cells and diminished trogocytosis to autologous lymphocytes in patients with SLE [ 41 ]. Many studies have demonstrated that PMNs and lymphocytes coexist and can interact at sites of chronic inflammation, infection, or allergic reactions in vivo [ 13 , 29 – 32 ].…”

Section: Discussionsupporting

confidence: 91%

Membrane Transfer from Mononuclear Cells to Polymorphonuclear Neutrophils Transduces Cell Survival and Activation Signals in the Recipient Cells via Anti-Extrinsic Apoptotic and MAP Kinase Signaling Pathways

Shen

et al. 2016

PLoS ONE

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The biological significance of membrane transfer (trogocytosis) between polymorphonuclear neutrophils (PMNs) and mononuclear cells (MNCs) remains unclear. We investigated the biological/immunological effects and molecular basis of trogocytosis among various immune cells in healthy individuals and patients with active systemic lupus erythematosus (SLE). By flow cytometry, we determined that molecules in the immunological synapse, including HLA class-I and-II, CD11b and LFA-1, along with CXCR1, are exchanged among autologous PMNs, CD4+ T cells, and U937 cells (monocytes) after cell-cell contact. Small interfering RNA knockdown of the integrin adhesion molecule CD11a in U937 unexpectedly enhanced the level of total membrane transfer from U937 to PMN cells. Functionally, phagocytosis and IL-8 production by PMNs were enhanced after co-culture with T cells. Total membrane transfer from CD4+ T to PMNs delayed PMN apoptosis by suppressing the extrinsic apoptotic molecules, BAX, MYC and caspase 8. This enhancement of activities of PMNs by T cells was found to be mediated via p38- and P44/42-Akt-MAP kinase pathways and inhibited by the actin-polymerization inhibitor, latrunculin B, the clathrin inhibitor, Pitstop-2, and human immunoglobulin G, but not by the caveolin inhibitor, methyl-β-cyclodextrin. In addition, membrane transfer from PMNs enhanced IL-2 production by recipient anti-CD3/anti-CD28 activated MNCs, and this was suppressed by inhibitors of mitogen-activated protein kinase (PD98059) and protein kinase C (Rottlerin). Of clinical significance, decreased total membrane transfer from PMNs to MNCs in patients with active SLE suppressed mononuclear IL-2 production. In conclusion, membrane transfer from MNCs to PMNs, mainly at the immunological synapse, transduces survival and activation signals to enhance PMN functions and is dependent on actin polymerization, clathrin activation, and Fcγ receptors, while membrane transfer from PMNs to MNCs depends on MAP kinase and PKC signaling. Defective membrane transfer from PMNs to MNCs in patients with active systemic lupus erythematous suppressed activated mononuclear IL-2 production.

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Section: Discussionsupporting

confidence: 91%

Membrane Transfer from Mononuclear Cells to Polymorphonuclear Neutrophils Transduces Cell Survival and Activation Signals in the Recipient Cells via Anti-Extrinsic Apoptotic and MAP Kinase Signaling Pathways

Shen

et al. 2016

PLoS ONE

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“…ILT2 was found to be downregulated in both pDCs and cDCs from SLE patients [216]. Moreover, as the common ligand of these axes, HLA-G was found to be diminished in monocytes from SLE patients, and a compromised ability of these monocytes to inhibit the proliferation of autologous lymphocytes was also revealed [217].…”

Section: Co-signaling Axes In Dendritic Cells (Dcs) Relating To Slementioning

confidence: 99%

The Role of Immune Checkpoint Receptors in Regulating Immune Reactivity in Lupus

Wang

et al. 2019

Cells

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Immune checkpoint receptors with co-stimulatory and co-inhibitory signals are important modulators for the immune system. However, unrestricted co-stimulation and/or inadequate co-inhibition may cause breakdown of self-tolerance, leading to autoimmunity. Systemic lupus erythematosus (SLE) is a complex multi-organ disease with skewed and dysregulated immune responses interacting with genetics and the environment. The close connections between co-signaling pathways and SLE have gradually been established in past research. Also, the recent success of immune checkpoint blockade in cancer therapy illustrates the importance of the co-inhibitory receptors in cancer immunotherapy. Moreover, immune checkpoint blockade could result in substantial immune-related adverse events that mimic autoimmune diseases, including lupus. Together, immune checkpoint regulators represent viable immunotherapeutic targets for the treatment of both autoimmunity and cancer. Therefore, it appears reasonable to treat SLE by restoring the out-of-order co-signaling axis or by manipulating collateral pathways to control the pathogenic immune responses. Here, we review the current state of knowledge regarding the relationships between SLE and the co-signaling pathways of T cells, B cells, dendritic cells, and neutrophils, and highlight their potential clinical implications. Current clinical trials targeting the specific co-signaling axes involved in SLE help to advance such knowledge, but further in-depth exploration is still warranted.

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“…Rosado and coauthors ( 67 ) and Chen and coauthors ( 68 ) have shown higher sHLA-G and IL-10 levels in systemic lupus erythematosus (SLE) patients in comparison with healthy controls, while Rizzo and coauthors ( 69 ) have observed lower sHLA-G concentrations in SLE patients ( 70 ). Interesting, the analysis of monocytes and mature CD83 positive dendritic cells from SLE patients has evidenced a diminished expression of HLA-G in comparison with healthy controls ( 71 ), a lower HLA-G expression in response to IL-10 and a lower HLA-G trogocytosis from autologous monocytes compared with controls. Using the SNPs mapping approach, HLA-G gene is recognized as a novel independent locus for SLE ( 72 ).…”

Section: Hla-g and Rheumatologic Diseasesmentioning

confidence: 99%

HLA-G Molecules in Autoimmune Diseases and Infections

et al. 2014

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Human leukocyte antigen (HLA)-G molecule, a non-classical HLA-Ib molecule, is less polymorphic when compared to classical HLA class I molecules. Human leukocyte antigen-G (HLA-G) was first detected on cytotrophoblast cells at the feto-maternal interface but its expression is prevalent during viral infections and several autoimmune diseases. HLA-G gene is characterized by polymorphisms at the 3′ un-translated region and 5′ upstream regulatory region that regulate its expression and are associated with autoimmune diseases and viral infection susceptibility, creating an unbalanced and pathologic environment. This review focuses on the role of HLA-G genetic polymorphisms, mRNA, and protein expression in autoimmune conditions and viral infections.

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Expression and Functional Role of HLA-G in Immune Cells from Patients with Systemic Lupus Erythematosus

Cited by 19 publications

References 50 publications

Membrane Transfer from Mononuclear Cells to Polymorphonuclear Neutrophils Transduces Cell Survival and Activation Signals in the Recipient Cells via Anti-Extrinsic Apoptotic and MAP Kinase Signaling Pathways

Membrane Transfer from Mononuclear Cells to Polymorphonuclear Neutrophils Transduces Cell Survival and Activation Signals in the Recipient Cells via Anti-Extrinsic Apoptotic and MAP Kinase Signaling Pathways

The Role of Immune Checkpoint Receptors in Regulating Immune Reactivity in Lupus

HLA-G Molecules in Autoimmune Diseases and Infections

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