Cellular Inflammatory Responses in Sickle Cell Disease

Sickle cell disease (SCD) is caused by a point mutation in the beta-globin gene that leads to the production of an abnormal hemoglobin, HbS. HbS polymerizes and forms fibers when deoxygenated, causing the red blood cells to change their natural biconcave disc shape to an abnormal ‘sickle’ shape, making them more fragile and, ultimately, prompting the vaso-occlusive processes in the microvasculature that are characteristic of the disorder. SCD is associated with intravascular hemolysis and ischemia-reperfusion processes that trigger innate immune responses and cause a chronic inflammatory state. Consequent damage-associated molecular pattern (DAMP) release leads to endothelial dysfunction, activation and recruitment of blood cells to the vascular wall, thromboinflammatory processes, and oxidative stress, which all contribute to vaso-occlusive events and organ injury that are major complications of the disease.

Exploring the complex cellular interactions and molecular responses in immune cells that are triggered by HbS polymerization will provide novel pathophysiological insights and guide the development of more effective therapeutic strategies for modifying the clinical course of sickle cell disease.

This Research Topic aims to publish high-quality original research that highlights the interplay between inflammatory and immunological pathways in the pathogenesis of sickle cell disease. We welcome submissions focusing on, but not limited to:
• Characterization of inflammatory cells, cytokines, biomarkers and DAMPs in SCD
• Thromboinflammation and complement system activation in SCD
• Endothelial cell activation and dysfunction in SCD
• Roles of immune cell extracellular traps (NETs, EETs) in SCD pathophysiology
• Role of intravascular hemolysis in innate immune and inflammatory responses in SCD
• Role of hypoxia-reperfusion processes and oxidative stress in SCD pathophysiology
• Role of microbiota and intestinal permeability in sickle SCD pathophysiology
• Immunopathogenesis of vaso-occlusion
• Targeting inflammation/ immunity for the treatment and reversal of painful vaso-occlusive crisis
• Inflammasomes and SCD pathophysiology
• Targeting inflammation/ innate immune responses for preventing end-organ damage in SCD.
• Resolution of inflammation in SCD
• Hemopoietic stem cell transplantation and inflammatory responses in SCD
• Translational and clinical studies targeting inflammation and innate immune responses in patients with SCD
• Novel therapeutic targets in SCD

Nicola Conran is employed by the State University of Campinas. All other Topic Editors declare no competing interests with regards to the Research Topic subject.​