AB0030 Autoantibody Producing CD27-Cd38int Pre-Naive B Cells Have Deficient Capacity to Support CD4+ T Cell Activation in Healthy Individuals, but Exhibit Defective Functions in Systemic Lupus Erythematosus Patients

Systemic lupus erythematosus (SLE) is a serious disorder of immune regulation characterized by overproduction of autoantibodies, lupus nephritis, CD4+ T cell aberrant activation, and immune complex-mediated inflammation. The chronic graft vs. host disease (cGVHD) mouse model is a well-established model of SLE. Quercitrin is a natural compound found in Tartary buckwheat with a potential anti-inflammatory effect that is used to treat heart and vascular conditions. In our previous study, we determined that quercitrin is an immunosuppressant with beneficial effects in mouse models of immune diseases. We hypothesized that quercitrin could prevent lupus nephritis in the cGVHD mouse model by decreasing the production of autoantibodies and inflammatory cytokines, and reducing immune cell activation. cGVHD was induced by injecting DBA/2 spleen cells into the tail vein of BDF1 mice. The cGVHD mice exhibited significant proteinuria, which is a marker of nephritis. Quercitrin decreased the number of serum antibodies, CD4+ T cell activation, as well as the expression levels of T-bet, GATA-3, and selected cytokines. Moreover, quercitrin treatment decreased the expression of inflammatory genes and cytokines in the kidney, as well as in peritoneal macrophages. In addition, quercitrin inhibited LPS-induced cytokines as well as the phosphorylation of ERK, p38 MAPK, and JNK in Raw264.7 cells. Overall, quercitrin ameliorated the symptoms of lupus nephritis in the cGVHD mouse model, which may be due to the inhibition of CD4 T cell activation and anti-inflammatory effects on macrophages.

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Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus

Clinical & Experimental Immunology ◽

10.1111/cei.12657 ◽

2015 ◽

Vol 182 (1) ◽

pp. 1-13 ◽

Cited By ~ 15

Author(s):

J. P. Mackern-Oberti ◽

J. Obreque ◽

G. P. Méndez ◽

C. Llanos ◽

A. M. Kalergis

Keyword(s):

Systemic Lupus Erythematosus ◽

Carbon Monoxide ◽

T Cell ◽

T Cell Activation ◽

Lupus Erythematosus ◽

Cell Activation ◽

Systemic Lupus ◽

Target Organs

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MAP4K Family Kinases and DUSP Family Phosphatases in T-Cell Signaling and Systemic Lupus Erythematosus

Cells ◽

10.3390/cells8111433 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1433 ◽

Cited By ~ 7

Author(s):

Chuang ◽

Tan

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cells ◽

T Cell ◽

Cell Signaling ◽

T Cell Activation ◽

Lupus Erythematosus ◽

Cell Activation ◽

Therapeutic Targets ◽

T Cell Signaling ◽

Systemic Lupus

T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE), which is a severe autoimmune disease. In the past 60 years, only one new therapeutic agent with limited efficacy has been approved for SLE treatment; therefore, the development of early diagnostic biomarkers and therapeutic targets for SLE is desirable. Mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) and dual-specificity phosphatases (DUSPs) are regulators of MAP kinases. Several MAP4Ks and DUSPs are involved in T-cell signaling and autoimmune responses. HPK1 (MAP4K1), DUSP22 (JKAP), and DUSP14 are negative regulators of T-cell activation. Consistently, HPK1 and DUSP22 are downregulated in the T cells of human SLE patients. In contrast, MAP4K3 (GLK) is a positive regulator of T-cell signaling and T-cell-mediated immune responses. MAP4K3 overexpression-induced RORγt–AhR complex specifically controls interleukin 17A (IL-17A) production in T cells, leading to autoimmune responses. Consistently, MAP4K3 and the RORγt–AhR complex are overexpressed in the T cells of human SLE patients, as are DUSP4 and DUSP23. In addition, DUSPs are also involved in either human autoimmune diseases (DUSP2, DUSP7, DUSP10, and DUSP12) or T-cell activation (DUSP1, DUSP5, and DUSP14). In this review, we summarize the MAP4Ks and DUSPs that are potential biomarkers and/or therapeutic targets for SLE.

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Cytokine Overproduction, T-Cell Activation, and Defective T-Regulatory Functions Promote Nephritis in Systemic Lupus Erythematosus

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/457146 ◽

2010 ◽

Vol 2010 ◽

pp. 1-6 ◽

Cited By ~ 33

Author(s):

Marco Tucci ◽

Stefania Stucci ◽

Sabino Strippoli ◽

Francesco Silvestris

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cells ◽

B Cells ◽

T Cell Activation ◽

Lupus Erythematosus ◽

Cell Activation ◽

Cell Function ◽

Inflammatory Cells ◽

Systemic Lupus ◽

Regulatory Functions

Lupus nephritis (LN) occurs in more than one-third of patients with systemic lupus erythematosus. Its pathogenesis is mostly attributable to the glomerular deposition of immune complexes and overproduction of T helper- (Th-) 1 cytokines. In this context, the high glomerular expression of IL-12 and IL-18 exerts a major pathogenetic role. These cytokines are locally produced by both macrophages and dendritic cells (DCs) which attract other inflammatory cells leading to maintenance of the kidney inflammation. However, other populations including T-cells and B-cells are integral for the development and worsening of renal damage. T-cells include many pathogenetic subsets, and the activation of Th-17 in keeping with defective T-regulatory (Treg) cell function regards as further event contributing to the glomerular damage. These populations also activate B-cells to produce nephritogenic auto-antibodies. Thus, LN includes a complex pathogenetic mechanism that involves different players and the evaluation of their activity may provide an effective tool for monitoring the onset of the disease.

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