Platelets are important for the development of immune tolerance: Possible involvement of TGF-β in the mechanism.

Platelets have diverse roles in immune processes in addition to their key functions in haemostasis and thrombosis. Some studies imply that platelets may be possibly related to the immune tolerance induction. However, the role of platelets in the development of immune tolerance is not fully understood. The purpose of this study was to investigate the role of platelets in the development of regulatory mechanisms responsible for cutaneous inflammation using a mouse model of low zone tolerance (LZT). Mice were treated with 2,4,6-trinitro-1-chlorobenzene (TNCB) 8 times every other day for tolerance induction with administration of anti-platelet antibody or control antibody during the tolerance induction phase every 3 days. After the treatment for the tolerance induction, mice were sensitized and then challenged with TNCB. The contact hypersensitivity (CHS) was significantly decreased at 24 hours after challenge in the mice with LZT than in those without LZT. Platelet depletion via administration of anti-platelet antibody reversed the inhibition of CHS and reduced the frequency of Foxp3+ Tregs in the inflamed skin and draining lymph nodes in mice with LZT. In addition, repeated low-dose skin exposure resulted in elevated plasma levels of transforming growth factor (TGF)-β1. Interestingly, platelet depletion reduced plasma TGF-β1 levels of mice with LZT. Furthermore, the CHS response was reduced by administration of recombinant TGF-β1 during platelet depletion in mice with LZT. Administration of anti-TGF-β antibody reversed the inhibition of the CHS responses. These results suggest that platelets are involved in the induction of immune tolerance via the release of TGF-β1.