Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis.

IL-17 and IL-23 are known to be absolutely central to psoriasis pathogenesis because drugs targeting either cytokine are highly effective treatments for this disease. The efficacy of these drugs has been attributed to blocking the function of IL-17-producing T cells and their IL-23-induced expansion. However, we demonstrate that mast cells and neutrophils, not T cells, are the predominant cell types that contain IL-17 in human skin. IL-17(+) mast cells and neutrophils are found at higher densities than IL-17(+) T cells in psoriasis lesions and frequently release IL-17 in the process of forming specialized structures called extracellular traps. Furthermore, we find that IL-23 and IL-1ß can induce mast cell extracellular trap formation and degranulation of human mast cells. Release of IL-17 from innate immune cells may be central to the pathogenesis of psoriasis, representing a fundamental mechanism by which the IL-23-IL-17 axis mediates host defense and autoimmunity.

Netting neutrophils induce endothelial damage, infiltrate tissues, and expose immunostimulatory molecules in systemic lupus erythematosus.

An abnormal neutrophil subset has been identified in the PBMC fractions from lupus patients. We have proposed that these low-density granulocytes (LDGs) play an important role in lupus pathogenesis by damaging endothelial cells and synthesizing increased levels of proinflammatory cytokines and type I IFNs. To directly establish LDGs as a distinct neutrophil subset, their gene array profiles were compared with those of autologous normal-density neutrophils and control neutrophils. LDGs significantly overexpress mRNA of various immunostimulatory bactericidal proteins and alarmins, relative to lupus and control neutrophils. In contrast, gene profiles of lupus normal-density neutrophils do not differ from those of controls. LDGs have heightened capacity to synthesize neutrophils extracellular traps (NETs), which display increased externalization of bactericidal, immunostimulatory proteins, and autoantigens, including LL-37, IL-17, and dsDNA. Through NETosis, LDGs have increased capacity to kill endothelial cells and to stimulate IFN-α synthesis by plasmacytoid dendritic cells. Affected skin and kidneys from lupus patients are infiltrated by netting neutrophils, which expose LL-37 and dsDNA. Tissue NETosis is associated with increased anti-dsDNA in sera. These results expand the potential pathogenic roles of aberrant lupus neutrophils and suggest that dysregulation of NET formation and its subsequent responses may play a prominent deleterious role.

Dear Doctor: a tool to facilitate patient-centered communication.

BACKGROUND: Patient-centered care has been identified as 1 of the 6 aims for the 21st century healthcare system. The notepad is a simple tool for reminders and personal interactions. We introduced Dear Doctor (DD) notes, a bedside notepad designed to prompt patient questions and improve patient satisfaction. OBJECTIVE: To provide DD notes as a bedside tool to facilitate patient communication and improve patient encounters with physicians in the hospital. DESIGN: This is a single-center, cross-sectional survey. METHODS: Over a 3-month period (July 2009-September 2009), all hospitalized patients in the intervention group (1 general medicine and 1 cardiology unit) at a large academic medical center received a DD notepad, a pen, and instructions on its use. We surveyed patients who received the DD notes on the intervention group (n = 440) and compared their responses to those from a matched control group (1 general medicine and 1 cardiology unit, n = 224). RESULTS: Of the 440 patients surveyed in the intervention group, 78% (n = 343) received the notepads in their rooms and 47% (n = 207) used them. Of the 343 patients who received the DD notepads, 65% (n = 223) reported that they took notes related to their hospital stay compared to only 22% of 224 patients (n = 50) in the control group (P < 0.001). The 207 patients using the DD notes had their questions more often answered by their physicians as measured on a 5-point Likert scale, compared to the control group (4.63 vs 4.45; P < 0.001). However, overall rating of communication did not differ between intervention and control groups in an intention-to-treat analysis (4.55 vs 4.55, P = 0.89). All patients who used the DD notepads responded on the survey that communication with their physicians was enhanced to at least some degree. CONCLUSIONS: Utilizing a bedside notepad improved patients' satisfaction with physician communication. A simple, low-cost, patient-centered tool such as the DD notes may enhance a patient's overall experience with their providers and the hospital.