SLAMF molecules are involved in the expression and regulation of multiple aspects of the innate and adaptive immune response. Work in mice carried out under the auspices of this Program have revealed important roles in the expression of autoimmunity, and more importantly, lupus-related pathology. Interestingly, disputed SLAMF-linked single nucleotide polymorphism (SNP) associations have been reported in patients with systemic lupus erythematosus (SLE) while the expression of SLAMF isoforms and their modulatory role on immune cell function has not been studied systematically. We hypothesize that the expression of isoforms of SLAMF is aberrant in Immune cells in SLE patients and that their homotypic engagement leads to aberrant immune cell function including cytokine and autoantibody production. To test this hypothesis we propose experiments grouped in four Specific Alms.
The significance of the proposed work is that it points out to the need to consider blockade of the homotypic SLAMF Interaction to suppress autoimmunity. This project borrows concepts from Projects 1 and 2 and provides direct feedback for murine preclinical studies.
|Comte, Denis; Karampetsou, Maria P; Yoshida, Nobuya et al. (2017) Signaling Lymphocytic Activation Molecule Family Member 7 Engagement Restores Defective Effector CD8+ T Cell Function in Systemic Lupus Erythematosus. Arthritis Rheumatol 69:1035-1044|
|Comte, Denis; Karampetsou, Maria P; Kis-Toth, Katalin et al. (2017) Brief Report: CD4+ T Cells From Patients With Systemic Lupus Erythematosus Respond Poorly to Exogenous Interleukin-2. Arthritis Rheumatol 69:808-813|
|Karampetsou, Maria P; Comte, Denis; Kis-Toth, Katalin et al. (2016) Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production. J Immunol 196:4915-24|
|Cuenca, Marta; Romero, Xavier; Sintes, Jordi et al. (2016) Targeting of Ly9 (CD229) Disrupts Marginal Zone and B1 B Cell Homeostasis and Antibody Responses. J Immunol 196:726-37|
|Kis-Toth, Katalin; Comte, Denis; Karampetsou, Maria P et al. (2016) Selective Loss of Signaling Lymphocytic Activation Molecule Family Member 4-Positive CD8+ T Cells Contributes to the Decreased Cytotoxic Cell Activity in Systemic Lupus Erythematosus. Arthritis Rheumatol 68:164-73|
|Comte, Denis; Karampetsou, Maria P; Kis-Toth, Katalin et al. (2016) Engagement of SLAMF3 enhances CD4+ T-cell sensitivity to IL-2 and favors regulatory T-cell polarization in systemic lupus erythematosus. Proc Natl Acad Sci U S A 113:9321-6|
|McArdel, Shannon L; Brown, Daniel R; Sobel, Raymond A et al. (2016) Anti-CD48 Monoclonal Antibody Attenuates Experimental Autoimmune Encephalomyelitis by Limiting the Number of Pathogenic CD4+ T Cells. J Immunol 197:3038-3048|
|McArdel, Shannon L; Terhorst, Cox; Sharpe, Arlene H (2016) Roles of CD48 in regulating immunity and tolerance. Clin Immunol 164:10-20|
|Wang, Ninghai; Keszei, Marton; Halibozek, Peter et al. (2016) Slamf6 negatively regulates autoimmunity. Clin Immunol 173:19-26|
|Chaudhary, Anu; Leite, Mara; Kulasekara, Bridget R et al. (2016) Human Diversity in a Cell Surface Receptor that Inhibits Autophagy. Curr Biol 26:1791-801|
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