Regulation of lymph node vascular growth by dendritic cells.

Lymph nodes grow rapidly and robustly at the initiation of an immune response, and this growth is accompanied by growth of the blood vessels. Although the vessels are critical for supplying nutrients and for controlling cell trafficking, the regulation of lymph node vascular growth is not well understood. We show that lymph node endothelial cells begin to proliferate within 2 d of immunization and undergo a corresponding expansion in cell numbers.

Selective regulation of IL-10 signaling and function by zymosan.

Balanced activity of pro- and anti-inflammatory cytokines during innate immune responses is required to allow effective host defense while avoiding tissue damage and autoimmunity. Induction of cytokine production after recognition of pathogen-associated molecular patterns (PAMPs) by innate immune cells has been well demonstrated, but modulation of cytokine function by PAMPs is not well understood. In this study we show that stimulation of macrophages with zymosan, which contains PAMPs derived from yeast, rapidly extinguished macrophage responses to IL-10, a suppressive cytokine that limits inflammatory tissue damage but also compromises host defense.

TLR2 and MyD88 contribute to Lactobacillus casei extract-induced focal coronary arteritis in a mouse model of Kawasaki disease.

Background: Kawasaki disease is the most common cause of acquired cardiac disease and acute vasculitis in children, targets the coronary arteries, and can occasionally be fatal. The pathogenesis and the molecular mechanisms remain unknown. After injection of Lactobacillus casei cell-wall extract (LCCWE), mice develop a focal coronary arteritis that histopathologically resembles Kawasaki disease, but the mechanism remains unclear.

Mature dendritic cells readily break tolerance in normal mice but do not lead to disease expression.

Objective: To examine the ability of mature dendritic cells (DCs) or macrophages intentionally exposed to lipopolysaccharide or apoptotic or necrotic cells to break tolerance in normal mice.

Methods: We adoptively transferred into C57BL/6 mice a variety of syngeneic myeloid antigen-presenting cell populations exposed to different activation stimuli as well as to meals of necrotic and apoptotic cells. We studied expression of autoimmunity in the immunized mice by serologic evaluation of autoantibody production, subclass analysis of Ig production, clinical evidence of kidney disease, glomerular immune complex deposition, and renal pathology.

Clinical trials in pediatric uveitis.

Uveitis associated with juvenile rheumatoid arthritis is the most common form of ocular inflammation in children. Prevention of permanent visual damage by this silent disease requires heightened awareness from pediatric rheumatologists and ophthalmologists. Early prediction of severity and prognosis will aid in the identification of those patients requiring more aggressive management.

Novel therapies for the treatment of juvenile rheumatoid arthritis (juvenile idiopathic arthritis).

The majority of children with juvenile idiopathic arthritis respond well to conventional treatment. However, some children will have a more aggressive disease course and will be resistant to standard management. Over the past 20 years, growth in our understanding of the immunopathogenesis of juvenile idiopathic arthritis and related diseases has facilitated significant therapeutic advances.