Review
Version 1
Preserved in Portico This version is not peer-reviewed
PKCδ Protects Against Lupus Autoimmunity
Version 1
: Received: 15 April 2024 / Approved: 16 April 2024 / Online: 16 April 2024 (15:54:16 CEST)
A peer-reviewed article of this Preprint also exists.
Chavan, S.V.; Desikan, S.; Roman, C.A.J.; Huan, C. PKCδ Protects against Lupus Autoimmunity. Biomedicines 2024, 12, 1364. Chavan, S.V.; Desikan, S.; Roman, C.A.J.; Huan, C. PKCδ Protects against Lupus Autoimmunity. Biomedicines 2024, 12, 1364.
Abstract
Protein Kinase C delta (PKCδ) has emerged as a key protective molecule against systemic lupus erythematosus (SLE or lupus), an autoimmune disease characterized by anti-double stranded (ds) DNA IgGs. Although PKCδ deficient mice and lupus patients with mutated PRKCD genes clearly demonstrate the requirement of PKCδ for preventing lupus autoimmunity, this critical tolerance mechanism remains poorly understood. We recently reported that PKCδ selectively deletes anti-dsDNA B cells in the germinal center (GC), disclosing a key B cell tolerance mechanism that prevents lupus autoimmunity. PKCδ’s tolerance function is activated by sphingomyelin synthase 2 (SMS2), a lipid enzyme whose expression is generally reduced in B cells from lupus patients. Moreover, pharmacologic strengthening of the SMS2/PKCδ tolerance pathway alleviated lupus pathogenesis in mice. Here, we review relevant publications in order to provide mechanistic insights into PKCδ’s tolerance activity, and discuss the potential significance of therapeutically targeting PKCδ’s tolerance activity in the GC for selectively inhibiting lupus autoimmunity.
Keywords
PKCδ; lupus; B cell tolerance; autoimmunity; SMS2
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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