2011
DOI: 10.1084/jem.20101653
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A novel isoform of the Ly108 gene ameliorates murine lupus

Abstract: The expression of the new Ly108 isoform H1 weakens lupus-like disease of C57BL/6.Sle1b mice.

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Cited by 54 publications
(98 citation statements)
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“…This interpretation is consistent with the finding of functional isoforms of several SLAMF genes with antagonistic activities (8,12,13,44). SLAMF6, LY9, and CD244 are differentially expressed on the surface of a wide variety of hematopoietic cells, including CMV-permissive macrophages and dendritic cells, and effector NK and cytotoxic CD8 ϩ T cells known to play a central role in the control of CMV infection.…”
Section: Discussionsupporting
confidence: 89%
See 1 more Smart Citation
“…This interpretation is consistent with the finding of functional isoforms of several SLAMF genes with antagonistic activities (8,12,13,44). SLAMF6, LY9, and CD244 are differentially expressed on the surface of a wide variety of hematopoietic cells, including CMV-permissive macrophages and dendritic cells, and effector NK and cytotoxic CD8 ϩ T cells known to play a central role in the control of CMV infection.…”
Section: Discussionsupporting
confidence: 89%
“…Engagement of the N-terminal Ig domains of SLAMF receptors with their cognate ligands results in the recruitment of these intracellular molecules, leading to signaling transduction events that ultimately modulate several immune responses (7,11). Moreover, coexpression of distinct isoforms of the SLAMF receptors, e.g., alternative cytoplasmic tails of SLAMF1 (12) or functionally distinct isoforms of CD244 and SLAMF6 (8,13,14), further refines these responses.…”
mentioning
confidence: 99%
“…Subsequent experiments largely focused upon the role of Ly108 in this phenotype, for which differences in the expression of several splice variants of this gene have been noted. In autoimmune mouse strains, expression of Ly108-1 is increased, whereas Ly108-2 expression is decreased and Ly108-H1 is absent (24,25). We confirmed similarly altered expression of these splice variants in c1 congenic T cells (N. Talaei and J. Wither, unpublished observations).…”
Section: Discussionsupporting
confidence: 79%
“…We confirmed similarly altered expression of these splice variants in c1 congenic T cells (N. Talaei and J. Wither, unpublished observations). Notably, absence of a Ly108-H1 splice variant was shown to promote differentiation of IFN-g-producing T cells (25). Therefore, it is likely that this contributes to the enhanced production of IFN-g by c1 congenic T cells in T cell-DC cocultures (Fig.…”
Section: Discussionmentioning
confidence: 92%
“…Since functional defects in both T and B lymphocytes are required for ANA production, it is possible that dysregulation of Ly108 isoform downstream signaling (derived from T:B engagement) might lead to disruption of peripheral tolerance and triggering of the autoimmune process in SLE. A third protein isoform, Ly108-H1, which is absent in two lupus-prone congenic animals has been recently identified (Keszei et al, 2011b). Ly108-H1 is encoded by a splice variant of Ly108 that lacks both exons 7 and 8.…”
Section: Slamf Spliced Variants and Their Role In Autoimmunitymentioning
confidence: 99%