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Validation of lanthionine synthetase C-like 2 (LANCL2) as a therapeutic target for systemic lupus erythematosus

Andrew Leber, Raquel Hontecillas, Victoria Zoccoli-Rodriguez and Josep Bassaganya-Riera
J Immunol May 1, 2019, 202 (1 Supplement) 132.7;
Andrew Leber
1Landos Biopharma
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Raquel Hontecillas
1Landos Biopharma
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Victoria Zoccoli-Rodriguez
1Landos Biopharma
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Josep Bassaganya-Riera
1Landos Biopharma
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Abstract

Lanthionine synthetase C-like 2 (LANCL2) is a membrane receptor with downstream effects on immunity and metabolism including the differentiation of regulatory CD4+ T cells. Its natural ligand, abscisic acid (ABA), has been shown to be decreased in autoimmune and inflammatory disease. Given the implication of the LANCL2 pathway in autoimmune disease and the progression of LANCL2-specific ligands, such as BT-11, into clinical stage development, we assessed the role of LANCL2 in systemic lupus erythematosus (SLE). In a TLR7/8 resiquimod-induced model of SLE, the loss of LANCL2 significantly decreases survival (P = 0.0008) relative to wild-type, resulting in less than 10% survival and a greater than 60% reduction relative to wild-type. Similarly, LANCL2−/− displayed greater serum anti-dsDNA antibodies and higher proteinuria. Within spleens, the loss of LANCL2 resulted in greater IL-6 and TNF, higher proportions of T follicular helper cells and lower ratios of regulatory CD4+ T cells relative to IFNγ producing cells. The greater inflammation was also mirrored in transcriptional changes at the splenic level indicating a greater susceptibility to severe disease. These results merit further exploration into the implication of LANCL2 signaling in human SLE and characterization of the therapeutic efficacy of LANCL2-specific agonists for future SLE development. Thus, LANCL2 is a novel promising therapeutic target for SLE.

  • Copyright © 2019 by The American Association of Immunologists, Inc.
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The Journal of Immunology
Vol. 202, Issue 1 Supplement
1 May 2019
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Validation of lanthionine synthetase C-like 2 (LANCL2) as a therapeutic target for systemic lupus erythematosus
Andrew Leber, Raquel Hontecillas, Victoria Zoccoli-Rodriguez, Josep Bassaganya-Riera
The Journal of Immunology May 1, 2019, 202 (1 Supplement) 132.7;

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Validation of lanthionine synthetase C-like 2 (LANCL2) as a therapeutic target for systemic lupus erythematosus
Andrew Leber, Raquel Hontecillas, Victoria Zoccoli-Rodriguez, Josep Bassaganya-Riera
The Journal of Immunology May 1, 2019, 202 (1 Supplement) 132.7;
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Print ISSN 0022-1767        Online ISSN 1550-6606