Background and Purpose Intracerebral hemorrhage (ICH) is swiftly followed by an inflammatory response. A key component of this response is the recruitment of leukocytes into the brain, which promote neurological injury in rodent models. However, the mechanisms by which leukocytes transmigrate across the endothelium into the injured brain are unclear. The present study examines leukocyte adhesion molecules (α4 integrin, L-selectin, and αLβ2 integrin) on four leukocyte subtypes to determine which are important for leukocyte recruitment after ICH. Methods We used the blood injection mouse model of ICH, whereby 25 μl of blood were injected into the striatum. Flow cytometry was used to quantify leukocyte populations and adhesion molecule expression in brain and blood. An α4 integrin blocking antibody was administered to evaluate the contribution of α4 in leukocyte migration and neurological injury. Results α4 integrin was elevated on all leukocyte populations in brain after ICH, whereas L-selectin was unchanged and αLβ2 was increased only on T cells. Antagonism of α4 resulted in decreased leukocyte transmigration and lessened neurobehavioral disability. Conclusions α4 integrin is an important cell adhesion molecule involved in neuroinflammation following ICH.

Photosensitivity is a sensitivity to UV radiation (UVR) commonly found in systemic lupus erythematosus (SLE) patients who have cutaneous disease. Upon even ambient UVR exposure, patients can develop inflammatory skin lesions that can reduce the quality of life. Additionally, UVR-exposed skin lesions can be associated with systemic disease flares marked by rising autoantibody titers and worsening kidney disease. Why SLE patients are photosensitive and how skin sensitivity leads to systemic disease flares are not well understood, and treatment options are limited. In recent years, the importance of immune cell–stromal interactions in tissue function and maintenance is being increasingly recognized. In this review, we discuss SLE as an anatomic circuit and review recent findings in the pathogenesis of photosensitivity with a focus on immune cell–stromal circuitry in tissue health and disease.

Systemic juvenile idiopathic arthritis (SJIA) is a rare disease with distinct features not seen in other categories of juvenile idiopathic arthritis. In recent years, advances in the understanding of disease immunopathogenesis have led to improved targeted therapies with significant improvement in patient outcomes. Despite these advances, there remain subsets of SJIA with refractory disease and severe disease-associated complications. This review highlights existing options for treatment of refractory SJIA and explores potential future therapeutics for refractory disease. Key Points: Despite targeted Interleukin IL-1 and IL-6 inhibitors a subset of SJIA remains refractory to therapy. About 1 in 7 SJIA patients will be refractory to targeted IL-1 or IL-6 therapy. There is no current agreed upon definition for refractory SJIA and we propose in this review that refractory SJIA is presence of active systemic or arthritic features despite treatment with anti-IL-1 or anti-IL-6 therapy or disease requiring glucocorticoids for control beyond 6 months. SJIA disease associated complications include presence of associated macrophage activation syndrome (MAS), interstitial lung disease (ILD) or amyloidosis and management of each differs. Refractory SJIA treatment options currently include additional conventional synthetic disease modifying anti-rheumatic drugs (csDMARDS), biologic (bDMARDS), combination biologic therapy, targeted synthetic (tsDMARDS) or other immunomodulatory therapies.