The role of the SLAM-SAP signaling pathway in the modulation of CD4+ T cell responses

Vilar, Marçal; Frutuoso, Mércia S.; Arruda, Sérgio; Lima, Danielle Malta; Bezerra, Cristianne Sousa; Pompeu, Margarida M. L.

doi:10.1590/s0100-879x2011007500038

Cited by 6 publications

(7 citation statements)

References 56 publications

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“…SAP proteins contribute to SLAM receptor activation as they mediate dimerization of SLAM receptors. SAP proteins have been reported to promote Th1 and Th2 differentiation (38-42). Our observation that SAP blockade with SAP siRNA results in significantly reduced IL-17 expression from T cells suggests a key role for SAP as a common proximal signal in SLAM-promoted IL-17 production.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of SLAM Receptors SLAMF3 and SLAMF6 in Systemic Lupus Erythematosus T Lymphocytes Promotes Th17 Differentiation

Chatterjee

Rauen

Kis-Tóth

et al. 2012

The Journal of Immunology

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Altered T cell function in systemic lupus erythematosus (SLE) is determined by various molecular and cellular abnormalities including increased IL-17 production. Recent evidence suggests a crucial role for signaling lymphocyte activation molecules (SLAMs) in the expression of autoimmunity. In this report, we demonstrate that SLAMF3 and SLAMF6 expression is increased on the surface of SLE T cells compared to normal cells. SLAM co-engagement with CD3 under Th17 polarizing conditions results in increased IL-17 production. SLAMF3 and SLAMF6 T cell surface expression and IL-17 levels significantly correlate with disease activity in SLE patients. Both naïve and memory CD4+ T cells produce more IL-17 in response to SLAM co-stimulation as compared to CD28 co-stimulation. In naïve CD4+ cells, IL-17 production after CD28 co-stimulation peaks on day 3, whereas co-stimulation with anti-SLAMF3 and anti-SLAMF6 antibodies results in a prolonged and yet increasing production over 6 days. Unlike co-stimulation with anti-CD28, SLAM co-stimulation requires the presence of the adaptor molecule SLAM-associated protein (SAP). Thus, engagement of SLAMF3 and SLAMF6 along with antigen-mediated CD3/TCR stimulation represents an important source of IL-17 production and disruption of this interaction with decoy receptors or blocking antibodies should mitigate disease expression in SLE and other autoimmune conditions.

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Section: Discussionmentioning

confidence: 99%

Increased Expression of SLAM Receptors SLAMF3 and SLAMF6 in Systemic Lupus Erythematosus T Lymphocytes Promotes Th17 Differentiation

Chatterjee

Rauen

Kis-Tóth

et al. 2012

The Journal of Immunology

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“…SLAM is mainly expressed in thymus cells, B cells, activated T cells, dendritic cells, macrophages, and activated mononuclear cells [23][24][25]. Stimulating TCR activation can induce the expression of SLAM in immune cells; then, SLAM amplifies TCR signaling [26,27]. After tyrosine phosphorylation of the immunoreceptor tyrosine-based switch motif (ITSM) in the intracellular domain of SLAM, the SLAM-SAP-Fyn compound is formed and then initiates intracellular signal transduction [28,29].…”

Section: Introductionmentioning

confidence: 99%

SLAM/SAP Decreased Follicular Regulatory T Cells in Patients with Graves’ Disease

Geng

Yang

Tang

et al. 2021

Journal of Immunology Research

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Signaling lymphocytic activation molecule (SLAM) and SLAM-associated protein (SAP) play important role in inflammatory and autoimmune diseases. Our study is aimed at detecting the expression of SLAM and SAP in patients with Graves’ disease (GD) and analyzing the effect of SLAM/SAP on circulating blood CD4+CXCR5+Foxp3+ follicular regulatory T (Tfr) cells. The level of SAP in CD4+CXCR5+ T cells and the level of SLAM on CD19+ B cells were significantly increased in the patients with GD, but no significant difference in the level of SLAM on CD4+CXCR5+ T cells was observed between the patients with GD and the healthy controls. A decrease in the percentage of Foxp3+ cells in CD4+CXCR5+ T cells was observed following anti-SLAM treatment, but the percentages of IFN-γ+ cells, IL-4+ cells, and IL-17+ cells showed no obvious differences. The proportion of circulating Tfr cells was decreased in the patients with GD, and the proportion of circulating Tfr cells had a negative correlation with the level of SAP in CD4+CXCR5+ T cells and the levels of autoantibodies in the serum of the patients with GD. Our results suggested that the SLAM/SAP signaling pathway is involved in the decrease of circulating Tfr cells in Graves’ disease.

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“…SLAM is mainly expressed in thymus cells, B cells, activated T cells, dendritic cells, macrophages, and activated mononuclear cells [23][24][25] . Stimulating TCR activation can induce the expression of SLAM in immune cells; then, SLAM ampli es TCR signaling [26,27] . After tyrosine phosphorylation of the immunoreceptor tyrosine-based switch motif (ITSM) in the intracellular domain of SLAM, the SLAM-SAP-Fyn compound is formed and then initiates intracellular signal transduction [28,29] .…”

Section: Introductionmentioning

confidence: 99%

“…The SLAM-SAP signaling pathway has been reported to induce the synthesis of Th2 cytokines and decrease the Th1 immune response [27] . Moreover, SAP de ciency damages the germinal center and reduces the number of antigen-speci c memory B cells and plasma cells [30,31] .…”

Section: Introductionmentioning

confidence: 99%

SLAM/SAP Decreased Follicular Regulatory T Cells in Patients With Graves’ Disease 

Geng

Yang

Tang

et al. 2021

Preprint

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Background: Signaling lymphocytic activation molecule (SLAM) and SLAM-associated protein (SAP) play important role in inflammatory and autoimmune diseases. Our study aimed to detect the expression of SLAM and SAP in patients with Graves’ disease (GD) and analyze the effect of SLAM/SAP on circulating blood CD4+CXCR5+ Foxp3+ follicular regulatory T (Tfr) cells.Methods: The expression of SLAM and SAP was assessed by flow cytometry and real-time PCR. The percentages of IFN-γ+ cells, IL-4+ cells, IL-17+ cells and Foxp3+ cells in CD4+CXCR5+ T cells and circulating CD4+CXCR5+ Foxp3+ Tfr cells after treatment with anti-SLAM and anti-CD3 antibodies were also assessed by flow cytometry. The correlations between the percentages of Tfr cells and the levels of autoantibodies as well as SAP were analyzed.Results: The level of SAP in CD4+CXCR5+ T cells and the level of SLAM on CD19+ B cells were significantly increased in the patients with GD, but no significant difference in the level of SLAM on CD4+CXCR5+ T cells was observed between the patients with GD and the healthy controls. A decrease in the percentage of Foxp3+ cells in CD4+CXCR5+ T cells was observed following anti-SLAM treatment, but the percentages of IFN-γ+ cells, IL-4+ cells and IL-17+ cells showed no obvious differences. The proportion of circulating Tfr cells was decreased in the patients with GD, and the proportion of circulating Tfr cells had a negative correlation with the level of SAP in CD4+CXCR5+ T cells and the levels of autoantibodies in the serum of the patients with GD.Conclusions: Our results indicate that the SLAM/SAP signaling pathway regulates Tfr cells, which may be involved in the pathogenesis of Graves’ disease.

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The role of the SLAM-SAP signaling pathway in the modulation of CD4+ T cell responses

Cited by 6 publications

References 56 publications

Increased Expression of SLAM Receptors SLAMF3 and SLAMF6 in Systemic Lupus Erythematosus T Lymphocytes Promotes Th17 Differentiation

Increased Expression of SLAM Receptors SLAMF3 and SLAMF6 in Systemic Lupus Erythematosus T Lymphocytes Promotes Th17 Differentiation

SLAM/SAP Decreased Follicular Regulatory T Cells in Patients with Graves’ Disease

SLAM/SAP Decreased Follicular Regulatory T Cells in Patients With Graves’ Disease

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The role of the SLAM-SAP signaling pathway in the modulation of CD4+ T cell responses

Cited by 6 publications

References 56 publications

Increased Expression of SLAM Receptors SLAMF3 and SLAMF6 in Systemic Lupus Erythematosus T Lymphocytes Promotes Th17 Differentiation

Increased Expression of SLAM Receptors SLAMF3 and SLAMF6 in Systemic Lupus Erythematosus T Lymphocytes Promotes Th17 Differentiation

SLAM/SAP Decreased Follicular Regulatory T Cells in Patients with Graves’ Disease

SLAM/SAP&nbsp;Decreased Follicular Regulatory T Cells in Patients With Graves’ Disease&nbsp;

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SLAM/SAP Decreased Follicular Regulatory T Cells in Patients With Graves’ Disease