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Related Concept Videos

Autoimmune Disorders01:29

Autoimmune Disorders

412
Autoimmune diseases are a group of disorders in which the body's immune system mistakenly attacks its own cells, tissues, and organs. This results from an overactive immune response against substances and tissues normally present in the body. Let's delve into the concept and mechanism of autoimmune diseases from an immune system point of view, explore different causes and examples of such diseases, and discuss potential solutions.
Concept and Mechanism of Autoimmune Diseases
The immune...
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The immunomodulatory effect of oral NaHCO<sub>3</sub> is mediated by the splenic nerve: multivariate impact revealed by artificial neural networks.

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PKCδ Protects against Lupus Autoimmunity.

Sailee Vijay Chavan1, Shreya Desikan1, Christopher A J Roman2

  • 1Program in Molecular and Cellular Biology, The School of Graduate Studies, State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, NY 11203, USA.

Biomedicines
|June 27, 2024
PubMed
Summary

Protein kinase C delta (PKCδ) protects against lupus by eliminating harmful B cells. Activating this pathway, often reduced in patients, offers a potential therapeutic strategy for autoimmune disease.

Keywords:
B cell tolerancePKCδSMS2autoimmunitylupus

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Area of Science:

  • Immunology
  • Molecular Biology
  • Autoimmunity

Background:

  • Systemic lupus erythematosus (SLE) is an autoimmune disease driven by autoantibodies, particularly anti-dsDNA IgGs.
  • Protein kinase C delta (PKCδ) is a critical regulator of immune tolerance, but its precise role in preventing lupus is not fully understood.
  • Reduced sphingomyelin synthase 2 (SMS2) expression in B cells is observed in lupus patients, potentially impairing PKCδ function.

Purpose of the Study:

  • To review and provide mechanistic insights into the B cell tolerance activity of PKCδ.
  • To discuss the therapeutic potential of targeting the SMS2/PKCδ pathway in the germinal center (GC) for SLE treatment.

Main Methods:

  • Review of relevant scientific literature on PKCδ, SMS2, and B cell tolerance in SLE.
  • Analysis of the role of PKCδ in selective deletion of autoreactive B cells within the GC.
  • Examination of the impact of SMS2 expression levels on PKCδ activity and lupus pathogenesis.

Main Results:

  • PKCδ selectively deletes B cells producing anti-dsDNA antibodies in the GC, a key tolerance mechanism.
  • The tolerance function of PKCδ is activated by SMS2, an enzyme often downregulated in lupus B cells.
  • Pharmacological enhancement of the SMS2/PKCδ pathway reduced lupus severity in mouse models.

Conclusions:

  • PKCδ plays a vital role in preventing lupus autoimmunity by maintaining B cell tolerance.
  • Targeting the SMS2/PKCδ pathway in the GC represents a promising therapeutic strategy for selective inhibition of lupus autoimmunity.