Circadian Clock Protein CRY Regulates Autoimmunity

The circadian system regulates numerous physiological processes including the adaptive immune system. Here we show that mice deficient for the circadian genes Cry1 and Cry2, (DKO) display an autoimmune phenotype including higher serum IgG concentration, presence of serum anti-nuclear antibodies, precipitation of IgG, IgM and complement 3 in glomeruli, and massive infiltrations of leukocytes into the lung and kidney. Activation of Cry DKO splenic B cells elicited markedly enhanced and prolonged tyrosine phosphorylation of cellular proteins compared to cells from control mice, suggesting that over activation of the BCR signaling pathway may contribute to autoimmunity in the Cry DKO mice. Expression of C1q, deficiency of which contributes to the pathogenesis of Systemic lupus erythematosus (SLE), was significantly downregulated in Cry DKO B cells. This suggests that B cell development, BCR signaling pathway and C1q expression may be under direct circadian control and dysregulation of which contributes to autoimmunity.

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Cao Q, Zhao X, Bai J, Gery S, Sun H, Lin DC, Chen Q, Chen Z, Mack L, Yang H, Deng R, Shi X, Chong LW, Cho H, Xie J, Li QZ, Müschen M, Atkins AR, Liddle C, Yu RT, Alkan S, Said JW, Zheng Y, Downes M, Evans RM, Koeffler HP