CB2 RECEPTOR IS ONE OF THE REGULATORY FACTORS OF THE AGE- RELATED CHANGES IN IMMUNE MECHANISM

Abstract Background Aging is one of the important factor which regulates immunity. It is established in adolescence, whereas immunosenescence occurs in the old age. It is necessary to examine the changes in immune mechanisms during each period to consider what effects the immunity-decline in old age. Cannabinoid type 2 (CB2) receptor is known to be expressed throughout immune-related cells, and it has been reported to act as an inhibitory regulator of immune response. However, contribution of CB2 receptors to immunosenescence still remains unknown. Aims & Objectives This study focus on clarifying what CB2 signaling will do in context of systemic immune regulation from the perspective of age, by comprehensive analysis of immune cell behavior under presence or absence of CB2 activity. Methods We chose LPS-induced systemic inflammatory model to evoke immune activation. LPS (10 mg/kg) was given by i.p. to CB2-KO and WT controls of 5 different ages: 2 month-old to 6 month-old, one month apart. Spleen has been harvested from these mice 2 hours after the administration, and immunophenotyping by flow cytometry has been conducted. As a result, T/NKT and NK cell populations particularly increased in LPS-treated CB2-KO, whereas B cells and CD11chigh cell populations significantly decreased in same animals. Interestingly, such population change has only been seen in particular ages, which are between 2 and 4 months (Fig 1). This particular age range in mouse is equivalent to the 10s to 20s in human. Discussion & Conclusion Altogether, we found that CB2 signaling may affect LPS-mediated immune cell population change, particularly in specific age range that is young to mature adult. These results further suggest that CB2 signaling could be one of the key modulator of the immune system transition among age. Identification of the possibly-affected immune cells will be required, to confirm the detailed mechanism between CB2 activation and cell population fluctuations under aging.