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Circadian clock cryptochrome proteins regulate autoimmunity.

Qi Cao1,2, Xuan Zhao3, Jingwen Bai4,5

  • 1Department of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048; caodapi@gmail.com downes@salk.edu evans@salk.edu.

Proceedings of the National Academy of Sciences of the United States of America
|November 8, 2017
PubMed
Summary
This summary is machine-generated.

Mice lacking circadian clock genes Cry1 and Cry2 develop autoimmune diseases. Loss of CRY proteins disrupts B cell development, B cell receptor signaling, and C1q expression, contributing to autoimmunity.

Keywords:
B cell receptorautoimmunecryptochrome

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Area of Science:

  • Immunology
  • Chronobiology
  • Molecular Biology

Background:

  • The circadian system governs diverse physiological functions, including immune responses.
  • Circadian rhythms are crucial for maintaining immune homeostasis.

Purpose of the Study:

  • To investigate the role of circadian clock genes Cry1 and Cry2 in regulating immune responses and autoimmunity.
  • To elucidate the impact of CRY protein deficiency on B cell development, signaling, and associated autoimmune phenotypes.

Main Methods:

  • Generation and analysis of Cry1 and Cry2 double knockout (Cry DKO) mice.
  • Assessment of autoimmune phenotypes, including autoantibodies and immune cell infiltration.
  • Flow cytometry analysis of B cell populations and evaluation of B cell receptor (BCR) signaling pathways.
  • Measurement of C1q expression in B cells.

Main Results:

  • Cry DKO mice exhibited a pronounced autoimmune phenotype, characterized by elevated IgG, antinuclear antibodies, and immune complex deposition.
  • Significant leukocyte infiltration was observed in the lungs and kidneys of Cry DKO mice.
  • B cell development was altered, with decreased pre-B cells and increased mature B cells in bone marrow and peritoneal cavity.
  • Cry DKO B cells showed hyperactivated BCR signaling and significantly downregulated C1q expression.

Conclusions:

  • Circadian clock CRY proteins are essential regulators of B cell development, BCR signaling, and C1q expression.
  • Loss of CRY proteins leads to dysregulation of these pathways, contributing to the development of autoimmune diseases.
  • CRY proteins represent a potential therapeutic target for autoimmune disorders.