Blood 1 8 a U G U S T 2 0 1 1 I V O L U M E 1 1 8 , N U M B E R 7

Content Provider	Semantic Scholar
Author	Lm, Beaulieu Dh, Perlman Dudakov, Jarrod A. Brink, Marcel R. M. Van Den
Abstract	leading to aggregation and heterotypic aggregate formation as well as activation of the co-agulation pathway to form thrombi. This reaction could lead to a myriad of pathophysiologic events depending on the specific clinical setting , including unstable coronary syndromes or sepsis-induced vascular occlusion. The next step will be demonstrating the presence and importance of these pathways in vivo, particularly in clinical settings. Understanding the specific clinical role of the complex interaction between histones, platelets, and immune receptors will continue to add to our understanding of thrombotic disease and the interaction of inflammation and platelets. Conflict-of-interest disclosure: The authors declare no competing financial interests. ■ REFERENCES 1. Semeraro F, Ammollo CT, Morrissey JH, et al. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and 4. Stimulation of Toll-like receptor 2 in human platelets induces a thromboinflamma-tory response through activation of phosphoinositide 3-kinase. 4. Rumbaut RE, Bellera RV, Randhawa JK, et al. Endo-toxin enhances microvascular thrombosis in mouse cremas-ter venules via a TLR4-dependent, neutrophil-independent mechanism. et al. Immune versus thrombotic stimulation of platelets differentially regulates signalling pathways, intracellular protein-protein interactions , and alpha-granule release. In this issue of Blood, Zlotoff and colleagues demonstrate that despite relaxed entry requirements after irradiation and hematopoietic stem cell transplantation (HSCT), insufficient supply of bone marrow (BM) T-cell progenitors acts as a limiting factor to thymic reconstitution, 1 contributing toward delayed T-cell recovery. T he thymus contains no self-renewing T-cell progenitors, but instead relies on the importation of BM-derived precursors from the circulation. The identity of this blood-borne progenitor, and in particular the extent of its lineage commitment, remains elusive and even controversial. 2 However, mounting evidence suggests that there may actually be multiple progenitors with T lin-eage and thymic seeding capacity, which all contribute to thymopoiesis. 2,3 Interestingly, while the precise identity of the thymus-seeding T-cell progenitor remains contentious , the mechanism by which these cells gain entry to the thymus and differentiate into mature T cells has been surprisingly consistent (see figure). 4-6 Expression of several molecules had previously been postulated for their importance in this process; however, only recently have studies emerged, including others by Bhandoola and colleagues, that have offered significant insight into the molecular pathways of thymic importation. The receptor-ligand interactions between p-selectin glycoprotein ligand-1 (PSGL-1)/p-selectin, 7 CCL25/ CCR9, and CCL19-CCL21/CCR7 6-9 have all been identified as fundamental in this active process of thymic importation. Although in single …
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