Platelets promote allergic asthma through the expression of CD154

Abstract

Platelet activation is associated with multiple immune responses and the pathogenesis of various immune-related diseases. However, the exact role and the underlying mechanism of platelets in the progression of allergic asthma remain largely unclear. In this study, we demonstrate that during antigen sensitization, platelets can be activated by ovalbumin (OVA) aerosol via the upregulation of CD154 (CD40L) expression. Platelet transfer promoted allergic asthma progression by inducing more severe leukocyte infiltration and lung inflammation, elevated IgE production and strengthened T helper 2 (Th2) responses in asthma-induced mice. Accordingly, platelet depletion compromised allergic asthma progression. Cd154-deficient platelets failed to promote asthma development, indicating the requirement of CD154 for platelets to promote asthma progression. The mechanistic study showed that platelets inhibited the induction of Foxp3 1 regulatory T cells both in vivo and in vitro at least partially through CD154, providing an explanation for the increase of Th2 responses by platelet transfer. Our study reveals the previously unknown role of platelet CD154 in the promotion of asthma progression by polarizing Th2 responses and inhibiting regulatory T-cell generation and thus provides a potential clue for allergic disease interventions.

Role of platelets in allergic airway inflammation

“…Specifically, platelet depletion has been shown to reduce the allergen-induced infiltration of eosinophils, lymphocytes, monocytes/macrophages, and neutrophils into the lungs of rodents. 27,[36][37][38] In this regard circulating platelet-leukocyte complexes occur at far greater frequency after both spontaneous asthma attacks in a biphasic manner or after allergen challenge in the clinic (Fig 2). 13,17,37 The possible significance of these platelet-leukocyte complexes is presumably to act as a ''priming'' step to promote efficient leukocyte adhesion to the vascular endothelium because leukocytes attached to platelets display more of the aM subunit (CD11b) of the aMb2 integrin macrophage 1 antigen (CD11b/CD18) than circulating leukocytes not attached to platelets.…”

“…Therefore it is of considerable interest that a number of studies have reported that platelet depletion can reduce allergen-induced bronchoconstriction and allergen-induced BHR. 27,36 However, the precise mechanism or mechanisms of this platelet-dependent BHR are not fully understood.…”

“…4,48,55 Platelet CD40L has recently been reported to be involved in the promotion of allergic airways inflammation by polarizing T H 2 responses after allergen exposure. 36 It is now accepted that DCs are essential in asthma pathogenesis, where myeloid DCs become involved very early in the disease by inducing sensitization to inhaled antigen. 51,56,57 Increasingly, myeloid DCs are viewed as essential proinflammatory cells that induce effector cytokine production in primed T H 2 cells during airway inflammation.…”

The Clinical Significance of Complete Blood Count Parameters for Frequent Emergency Department Admissions and Re-hospitalisation in Patients with Asthma Attacks Requiring Hospitalisation

“…[29,30] CD154 release has been shown to activate platelets during allergen sensitization in asthma, stimulating other white blood cells to cause inflammation to become more pronounced. [31] In the literature, we could not find a study investigating the relationship between asthma attacks and platelet count and PLR. In our study, the platelets were not associated with frequent emergency admissions, whereas high PLR values were associated with severe episodes requiring hospitalization.…”

TIPE2 is negatively correlated with tissue factor and thrombospondin-1 expression in patients with bronchial asthma

“…Levels of coagulation parameters, platelets, fibrinogen, tissue factor, thromboxane A2, thrombin and activated protein C may reflect thrombosis formation during the pathophysiological process of asthma (5,6). Platelets activated by the up-regulation of cluster of differentiation 154 may release the platelet δ, α and λ granules, induce pulmonary inflammation and enhance the T helper cell 2 immune response, thus aggravating asthma severity (7). The extracellular signal-regulated kinase 1/2 signaling pathway serves an important role in the process of thrombus-promoting airway remodeling in ovalbumin allergic rats (8).…”