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

Abstract

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.

Dynamic EASIX scores closely predict nonrelapse mortality after allogeneic hematopoietic cell transplantation

“…Although GVHD has been linked to accelerated platelet destruction [23][24][25] and decreased production, platelets have been shown to be important for the induction of immune tolerance and regulatory T-cell function either directly through cell-cell interactions or via release of transforming growth factor-B1. 23,26 Furthermore, persistent thrombocytopenia after allo-HCT has been found to be a strong negative predictor of survival independent of GVHD, 27 which is not surprising given that many common contributors to NRM, such as sepsis, thrombotic microangiopathy, veno-occlusive disease/sinusoidal obstruction syndrome, and so on, involve endothelial damage and platelet consumption or destruction. Finally, thrombocytopenia is likely also associated with NRM through endothelium-independent mechanisms; given the high incidence of infectious-related deaths in our cohorts, viral infection and their therapies may have been confounders contributing to the association of high EASIX with NRM.…”

Exploitation of platelets for antitumor drug delivery and modulation of the tumor immune microenvironment

“…Similar studies in sepsis mouse models have shown that blocking the P2Y12 receptor with clopidogrel alleviates TGF-β elevation in the plasma and restrains Treg population growth in the spleen during sepsis [145]. Using an immune tolerance mouse model, Hotta et al [147] have shown that platelet depletion reverses the increase in Tregs in the inflamed skin and draining lymph nodes of mice via TGF-β release, and significantly enhances the contact hypersensitivity response tolerance of cutaneous inflammation. Furthermore, in a recent study, platelets have been observed to recruit neutrophils into the lungs during the onset of bacterial-induced pneumonia, and to recruit Tregs and transcriptionally reprogrammed alveolar macrophages to an anti-inflammatory phenotype during the resolution phase.…”

The EGF Motif With CXDXXXXYXCXC Sequence Suppresses Fibrosis in a Mouse Skin Wound Model

“…Wound healing is a long and complex process and begins with hemostasis (hemostasis phase). Platelets release many factors, including transforming growth factor-β1 (TGFβ1), which induces inflammatory cell migration (22). These inflammatory cells produce various cytokines (23).…”