Circadian protein CLK suppresses transforming growth factor-β expression in peripheral B cells of nurses with day-night shift rotation.

Background and aims: The mechanism of dysfunction of regulatory B cells is unclear. The circadian loco-motor output cycles kaput (CLK) regulates immune responses. CLK expression can be increased by alteration of the circadian rhythm. This study tests a hypothesis that alteration of the circadian rhythm, such as engaging the day-night-shift rotation (DNSR), interferes with the expression of transforming growth factor (TGF)-beta in B cells (TGFbB cell). Methods: Peripheral blood samples were collected from DNSR nurses and persons with the regular circadian clock life style (RC). The frequency of TGFbB cells in the blood samples was assessed by flow cytometry. The expression of TGF-beta in B cells was assessed with real time RT-PCR. Results: We observed that the frequency of peripheral TGFbB cells was less in DNSR nurses as compared to RC subjects. The expression of CLK and histone deacety-lase 11 in peripheral B cells was higher, the TGF-beta expression was lower, in peripheral B cells of DNSR nurses. Over-expression of CLK repressed the expression of TGF-beta in B cells, which was mediated by HDAC11. Conclusions: The CLK expression in peripheral B cells is higher in DNSR nurses, which suppresses the expression of TGF-beta in B cells. To regulate the expression of CLK during the circadian clock alteration needs to be further investigated.