Characterization of CD41+ cells in the lymph node.

Lymph nodes (LNs) are the critical sites of immunity, and the stromal cells of LNs are crucial to their function. Our understanding of the stromal compartment of the LN has deepened recently with the characterization of nontraditional stromal cells. CD41 (integrin αIIb) is known to be expressed by platelets and hematolymphoid cells. We identified two distinct populations of CD41+Lyve1+ and CD41+Lyve1- cells in the LNs. CD41+Lyve1- cells appear in the LN mostly at the later stages of the lives of mice. We identified CD41+ cells in human LNs as well. We demonstrated that murine CD41+ cells express mesodermal markers, such as Sca-1, CD105 and CD29, but lack platelet markers. We did not observe the presence of platelets around the HEVs or within proximity to fibroblastic reticular cells of the LN. Examination of thoracic duct lymph fluid showed the presence of CD41+Lyve1- cells, suggesting that these cells recirculate throughout the body. FTY720 reduced their trafficking to lymph fluid, suggesting that their egress is controlled by the S1P1 pathway. CD41+Lyve1- cells of the LNs were sensitive to radiation, suggestive of their replicative nature. Single cell RNA sequencing data showed that the CD41+ cell population in naïve mouse LNs expressed largely stromal cell markers. Further studies are required to examine more deeply the role of CD41+ cells in the function of LNs.

Pathophysiology of immune thrombocytopenia.

PURPOSE OF REVIEW: Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder with as of yet, no established clinical prognostic or diagnostic biomarkers. Patients frequently experience a markedly decreased quality of life and may be at risk for severe/fatal haemorrhage. Here, we address discoveries in the pathogenesis of ITP, and novel therapeutic strategies in mouse models and human patients. Consolidation of these findings should be important in providing insight to establish future prognostic protocols as well as cutting-edge therapeutics to target refractory ITP. RECENT FINDINGS: It is unknown why a significant portion of ITP patients are refractory to standard treatments. Recent findings suggest distinct heterogeneity in ITP including antibody-mediated platelet activation, Fc-independent desialylated platelet clearance, attenuation of platelet-mediated hepatic thrombopoietin generation, and decreased CD8 T-suppressor generation. These mechanisms may partially explain clinical observations of increased refractoriness to standard therapies targeting classical Fc-dependent pathways. Moreover, these have initiated investigations into platelet desialylation as a diagnostic/prognostic marker and therapeutic target. SUMMARY: Recent evidence of distinct ITP pathophysiology has opened new exploratory avenues for disease management. We will discuss the utility of investigations into these mechanisms of ITP and its potential impact in our understanding of pathogenesis and future treatment strategies.