Gut T cell-independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells.

The gut mounts secretory immunoglobulin A (SIgA) responses to commensal bacteria through nonredundant T cell-dependent (TD) and T cell-independent (TI) pathways that promote the establishment of mutualistic host-microbiota interactions. SIgAs from the TD pathway target penetrant bacteria, and their induction requires engagement of CD40 on B cells by CD40 ligand on T follicular helper cells. In contrast, SIgAs from the TI pathway bind a larger spectrum of bacteria, but the mechanism underpinning their production remains elusive. Here, we show that the intestinal TI pathway required CD40-independent B cell-activating signals from TACI, a receptor for the innate CD40 ligand-like factors BAFF and APRIL. TACI-induced SIgA responses targeted a fraction of the gut microbiota without shaping its overall composition. Of note, TACI was dispensable for TD induction of IgA in gut-associated lymphoid organs. Thus, BAFF/APRIL signals acting on TACI orchestrate commensal bacteria-specific SIgA responses through an intestinal TI program.

Therapeutic effect of urocortin and adrenomedullin in a murine model of Crohn's disease.

BACKGROUND AND AIMS: Urocortin 1 (UCN) and adrenomedullin (AM) are two recently discovered neuropeptides that, due to their distribution and binding to receptors in immune cells, have emerged as potential endogenous anti-inflammatory factors. Crohn's disease is a chronic debilitating disease characterised by a Th1 driven severe inflammation of the gastrointestinal tract. This study investigated the therapeutic effect of UCN and AM in a murine model of colitis. METHODS AND RESULTS: Treatment with UCN or AM ameliorated significantly the clinical and histopathological severity of the inflammatory colitis, abrogating body weight loss, diarrhoea, and inflammation, and increased the survival rate of colitic mice. The therapeutic effect was associated with downregulation of both inflammatory and Th1 driven autoimmune responses, including regulation of a wide spectrum of inflammatory mediators. In addition, partial involvement of interleukin 10 secreting regulatory cells in this therapeutic effect was demonstrated. Importantly, UCN or AM treatments were therapeutically effective in established colitis and avoided recurrence of the disease. CONCLUSIONS: This work identifies UCN and AM as two potent anti-inflammatory factors with the capacity to deactivate the intestinal inflammatory response and restore mucosal immune tolerance at multiple levels. Consequently, both peptides represent novel multistep therapeutic approaches for the treatment of Crohn's disease and other Th1 mediated inflammatory diseases.

Therapeutic approaches of vasoactive intestinal peptide as an immunomodulatory cytokine / Aproximaciones terapéuticas al péptido intestinal vasoactivo como una citocina inmunomoduladora

Vasoactive intestinal peptide (VIP) is a neuropeptide produced by the lymphoid cells, which exerts a wide spectrum of immunological functions controlling the homeostasis of immune system through different receptors expressed in various immunocompetent cells. During the last decade, VIP has been clearly identified as a potent anti-inflammatory factor, both in innate and adaptive immunity. In innate immunity, VIP inhibits the production of pro-inflammatory cytokines and chemokines from macrophages, microglia and dendritic cells. In addition, VIP reduces the expression of costimulatory molecules on the antigen-presenting cells, and therefore reduces the activation of antigen-specific CD4+ T cells. In terms of adaptive immunity, VIP promotes Th2-type responses, and reduces the pro-inflammatory Th1-type responses. Several of the molecular mechanisms involved in the inhibition of cytokine and chemokine expression, and in the preferential development and/or survival of Th2 effectors, are perfectly known. Therefore, VIP and its analogues have been recently proposed as very promising candidates, alternative to other existing treatments, for treating acute and chronic inflammatory and autoimmune diseases, such as septic shock, rheumatoid arthritis, multiple sclerosis, Parkinson’s disease, Crohn’s disease, or autoimmune diabetes. The aim of this review is firstly to update our knowledge of the cellular and molecular events relevant to VIP function on the immune system; and secondly to gather together recent data that support its role as a type 2 cytokine. Recognition of the central functions that VIP plays in cellular processes is focusing our attention on this «very important peptide» as exciting new candidates for therapeutic intervention and drug development (AU)

El Péptido Intestinal Vasoactivo (VIP) es un neuropéptido producido por diferentes células inmunitarias, con un amplio abanico de funciones implicadas en el control homeostático del sistema inmunitario. Estos efectos son llevados a cabo a través de varios receptores específicos expresados en distintas células inmunocompetentes. En la última década, se ha identificado a VIP como un potente factor anti-inflamatorio, tanto en la inmunidad innata como en la adquirida. En la inmunidad innata, VIP inhibe la producción de citocinas y quimiocinas proinflamatorias por macró- fagos, microglía y células dendríticas. Además, VIP reduce la expresión de moléculas coestimuladoras en las células presentadoras de antígeno, reduciendo así la estimulación antígeno-específica de células T. En cuanto a la inmunidad adquirida, VIP favorece las respuestas tipo Th2 frente a las proinflamatorias tipo Th1. Actualmente se conocen perfectamente muchos de los mecanismos moleculares y celulares implicados en esta regulación. Por lo tanto, se ha propuesto recientemente a VIP y análogos como candidatos muy prometedores, alternativos a terapias existentes, en el tratamiento de varias enfermedades autoinmunitarias e inflamatorias crónicas, tales como shock endotóxico, artritis reumatoide, esclerosis múltiple, enfermedad de Parkinson y de Crohn, y diabetes tipo I. El principal objetivo de esta revisión es primeramente actualizar nuestro conocimiento sobre los procesos celulares y moleculares relevantes en la función inmunitaria de VIP, y en segundo lugar, reunir todos los datos recientes que sustentan la hipótesis de que este «very important peptide» podría ser considerado una citocina tipo 2 candidato en el diseño futuro de nuevas terapias inmunomoduladoras (AU)

[The decentralization and municipalization of health services in Säo Paulo, Brazil]. / Descentralización y municipalización de los servicios de salud en São Paulo, Brasil.

The health system in Brazil has undergone profound changes since the 1980s. In the state of São Paulo, the processes of decentralization to the municipio and regional levels, as well as integration of health services, began in 1983. This study describes the strategies adopted by the Ministry of Health of the state of São Paulo to implement these processes and create 65 regional health offices, and discusses the role of these offices in the new unified health system. It is concluded that decentralization has resulted in increased local government participation in financing the health system, that production of medical and community health services has grown, and that health indicators have improved.

[Local health systems: challenges for the 90's]. / Los sistemas locales de salud: desafíos para la década de los noventa.

This article gives a general overview of present local health systems and their possible future. It reviews the background that led the countries of the Americas to make plans to transform their national health systems and points out the key role played by local health systems in this undertaking. In addition to summarizing the basic conditions necessary for setting up a local health system, the authors define these local systems as instruments for decentralization of the State and the expression of democratic action. They consider it an imperative for the 1990s to ensure that the services are improved in terms of equity and quality, democratization and social participation, economic and social development and transformation, and efficiency and use of appropriate technology. Stress is placed on the comprehensive concept of health, well-being, and development, as well as on health promotion by the population itself, while taking into account the responsibilities that correspond to national sector agencies and to local communities.

[Method for analyzing and estimating human resources for maternal and child care programs]. / Método para el análisis y la estimación de recursos humanos para los programas de atención maternoinfantil

This report described the version of the Human Resources Analysis and Estimation Method (MAERH) that was specially devised for analyzing maternal and child health and family planning personnel (the MAERH/AMI/1 version). The general features of the method are presented and its ability to analyze health programs and to estimate the human resources needed is emphasized. In addition, the operation and use of the method, its advantages and short-comings, as well as its development and possible adaptation to wider-ranging or more specific problems are described. Finally, the results obtained in the maternal and child health area of the State of Pernambuco, Brazil, are presented to exemplify the use of the method.

Método para el análisis y la estimación de recursos humanos para los programas de atención maternoinfantil / Method for analyzing and estimating human resources for maternal and child care programs

This report described the version of the Human Resources Analysis and Estimation Method (MAERH) that was specially devised for analyzing maternal and child health and family planning personnel (the MAERH/AMI/1 version). The general features of the method are presented and its ability to analyze health programs and to estimate the human resources needed is emphasized. In addition, the operation and use of the method, its advantages and short-comings, as well as its development and possible adaptation to wider-ranging or more specific problems are described. Finally, the results obtained in the maternal and child health area of the State of Pernambuco, Brazil, are presented to exemplify the use of the method (Au)