Publications by authors named "Jill M Mooney"

4 Publications

  • Page 1 of 1

The role of SAP and the SLAM family in autoimmunity.

Curr Opin Immunol 2006 Dec 29;18(6):656-64. Epub 2006 Sep 29.

Center for Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75235, USA.

The signaling lymphocyte activation molecule (SLAM) family of receptors and their associated signaling adaptors play a pivotal role in the regulation of various stages of cellular immunity. They regulate lymphocyte-lymphocyte interactions involved in both cell-mediated and humoral immune responses. Recent evidence indicates that members of this family of receptors and signaling intermediates are also involved in autoimmunity. These include strictly correlative studies showing increased expression of various family members in immune effectors involved in rheumatoid arthritis and in inflammatory bowel disease, as well as more direct evidence (from various knockout strains of mice) for their role in autoimmune processes such as experimental allergic encephalomyelitis and lupus. Additional studies defining naturally occurring polymorphic variations in the SLAM family show a direct role in initiating the break in tolerance that is an essential step in the progression towards autoimmunity.
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http://dx.doi.org/10.1016/j.coi.2006.09.010DOI Listing
December 2006

Regulation of B cell tolerance by the lupus susceptibility gene Ly108.

Science 2006 Jun;312(5780):1665-9

Department of Internal Medicine (Rheumatology), University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

The susceptibility locus for the autoimmune disease lupus on murine chromosome 1, Sle1z/Sle1bz, and the orthologous human locus are associated with production of autoantibody to chromatin. We report that the presence of Sle1z/Sle1bz impairs B cell anergy, receptor revision, and deletion. Members of the SLAM costimulatory molecule family constitute prime candidates for Sle1bz, among which the Ly108.1 isoform of the Ly108 gene was most highly expressed in immature B cells from lupus-prone B6.Sle1z mice. The normal Ly108.2 allele, but not the lupus-associated Ly108.1 allele, was found to sensitize immature B cells to deletion and RAG reexpression. As a potential regulator of tolerance checkpoints, Ly108 may censor self-reactive B cells, hence safeguarding against autoimmunity.
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http://dx.doi.org/10.1126/science.1125893DOI Listing
June 2006

The murine NK receptor 2B4 (CD244) exhibits inhibitory function independent of signaling lymphocytic activation molecule-associated protein expression.

J Immunol 2004 Sep;173(6):3953-61

Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas 75390, USA.

2B4 (CD244) is a receptor belonging to the CD2-signaling lymphocytic activation molecule family and is found on all murine NK cells and a subset of NKT and CD8+ T cells. Murine 2B4 is expressed as two isoforms (2B4 short and 2B4 long) that arise by alternative splicing. They differ only in their cytoplasmic domains and exhibit opposing function when expressed in the RNK-16 cell line. The ligand for 2B4, CD48, is expressed on all hemopoietic cells. Previous studies have shown that treatment of NK cells with a 2B4 mAb results in increased cytotoxicity and IFN-gamma production. In this report, we used CD48+/- variants of the P815 tumor cell line and 2B4 knockout mice to show that engagement of 2B4 by its counterreceptor, CD48, expressed on target cells leads to an inhibition in NK cytotoxicity. The addition of 2B4 or CD48 mAb relieves this inhibition resulting in enhanced target cell lysis. This 2B4-mediated inhibition acts independently of signaling lymphocytic activation molecule-associated protein expression. Imaging studies show that 2B4 preferentially accumulates at the interface between NK and target cells during nonlytic events also indicative of an inhibitory receptor. This predominant inhibitory function of murine 2B4 correlates with increased 2B4 long isoform level expression over 2B4 short.
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http://dx.doi.org/10.4049/jimmunol.173.6.3953DOI Listing
September 2004

Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis.

J Clin Invest 2003 Dec;112(12):1862-70

Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9034, USA.

Invasive aspergillosis is a severe pneumonia that is usually fatal despite currently available therapy. The disease disproportionately afflicts immunocompromised patients, indicating the critical importance of the immune status of the host in this infection, but the defense mechanisms against this pathogen remain incompletely understood. In the current study, we hypothesized that the chemokine ligand monocyte chemotactic protein-1, also designated CC chemokine ligand-2 (MCP-1/CCL2) is necessary for effective host defense against invasive aspergillosis in immunocompromised hosts. We found a rapid and marked induction of MCP-1/CCL2 in the lungs of neutropenic mice with invasive aspergillosis. Neutralizing MCP-1/CCL2 resulted in twofold greater mortality and greater than threefold increase in pathogen burden in the lungs. Neutralization of MCP-1/CCL2 also resulted in reduced recruitment of NK cells to the lungs at early time points, but did not affect the number of other leukocyte effector cells in the lungs. Ab-mediated depletion of NK cells similarly resulted in impaired defenses against the infection, resulting in a greater than twofold increase in mortality and impaired clearance of the pathogen from the lungs. These data establish MCP-1/CCL2-mediated recruitment of NK cells to the lungs as a critical early host defense mechanism in invasive aspergillosis and demonstrate NK cells to be an important and previously unrecognized effector cell in this infection.
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http://dx.doi.org/10.1172/JCI18125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC296992PMC
December 2003