Circadian protein CLOCK modulates regulatory B cell functions of nurses engaging day-night shift rotation.

ABSTRACT

Circadian rhythm proteins participate in regulating multiple physiological activities, including immune responses. The day-night shift rotation (DNSR) affects the circadian rhythm. The influence of circadian rhythm disturbance associated with DNSR on the regulatory functions of B cells remains to be studied. In this study, Blood samples were collected from 30 nurses engaging DNSR. The B cells were isolated from blood samples through magnetic cell separation. The regulatory function of IL-10 B cells (B10 cells) was evaluated using immunological assays. The results showed that the IL-10 expression was significantly reduced in B10 cells in nurses after DNSR. The capacity of inducing type 1 regulatory T cells (Tr1 cells) in B10 cells was down regulated. The circadian locomotor output cycles kaput (CLOCK) was increased in B10 cells, which was negatively correlated with the reduction of IL-10 expression in B10 cells. CLOCK formed a complex with c-Maf inducing protein (CMIP) to induce CMIP degradation; this restricted the IL10 gene transcription in B10 cells. B10 cells collected from nurses after DNSR were ineffective in suppressing T-cell proliferation and inducing Tr1 cells. In summary, DNSR affects the immune regulating function of B10 cells by disturbing the circadian rhythm.