The Transcription Factor NFATc2 Controls Apoptosis and Activation of T Cells by IL-6 in Colitis

The nuclear factor of activated T cells (NFAT) family of transcription factors controls calcium signaling in T lymphocytes. In this study, we have identified a crucial regulatory role of the transcription factor NFATc2 in T cell-dependent experimental colitis. Similar to ulcerative colitis in humans, the expression of NFATc2 was up-regulated in oxazolone-induced chronic intestinal inflammation. Furthermore, NFATc2 deficiency suppressed colitis induced by oxazolone administration. This finding was associated with enhanced T cell apoptosis in the lamina propria and strikingly reduced production of IL-6, -13, and -17 by mucosal T lymphocytes. Further studies using knockout mice showed that IL-6, rather than IL-23 and -17, are essential for oxazolone colitis induction. Administration of hyper-IL-6 blocked the protective effects of NFATc2 deficiency in experimental colitis, suggesting that IL-6 signal transduction plays a major pathogenic role in vivo. Finally, adoptive transfer of IL-6 and wild-type T cells demonstrated that oxazolone colitis is critically dependent on IL-6 production by T cells. Collectively, these results define a unique regulatory role for NFATc2 in colitis by controlling mucosal T cell activation in an IL-6-dependent manner. NFATc2 in T cells thus emerges as a potentially new therapeutic target for inflammatory bowel diseases.

Rapid death and regeneration of NKT cells in anti-CD3epsilon- or IL-12-treated mice: a major role for bone marrow in NKT cell homeostasis.

Natural killer T (NKT) cells express a T cell receptor (TCR) and markers common to NK cells, including NK1.1. In vivo, NKT cells are triggered by anti-CD3epsilon MAb to rapidly produce large amounts of IL-4 and by IL-12 to reject tumors. We show here that anti-CD3epsilon MAb treatment rapidly depletes the liver (and partially the spleen) of NKT cells and that homeostasis is achieved 1 to 2 days later via NKT cell proliferation that occurs mainly in bone marrow. Similar results were obtained in mice treated with IL-12. Collectively, our data demonstrate that peripheral NKT cells are highly sensitive to activation-induced cell death and that bone marrow plays a major role in restoring NKT cell homeostasis.

Reliure de : La Fabrica del mondo, di M. Francesco Alunno,... nella quale si contengono tutte le voci di Dante, del Petrarca, del Boccaccio et d'altri buoni autori...

Numérisation partielle de reliure

Ex XIIII. T. Livii Decadibus. Prima, tertia, quarta, in qua praeter fragmenta III, & X libri, quae in Germania nuper reperta, hic etiam continentur, multa adulterina expunximus, multa vera recepimus, quae in aliis non habentur. Epitome singulorum librorum XIIII Decadum. Historia omnium XIIII Decadum in compendium redacta ab L. Floro. Polybii lib. V de rebus Romanis latinitate donati à Nicolao Perotto. Index copiosissimus rerum omnium memorabilium...

[Histoire romaine (latin). 1518-1533]

Ex XIIII. T. Livii Decadibus. Prima, tertia, quarta, in qua praeter fragmenta III, & X libri, quae in Germania nuper reperta, hic etiam continentur, multa adulterina expunximus, multa vera recepimus, quae in aliis non habentur. Epitome singulorum librorum XIIII Decadum. Historia omnium XIIII Decadum in compendium redacta ab L. Floro. Polybii lib. V de rebus Romanis latinitate donati à Nicolao Perotto. Index copiosissimus rerum omnium memorabilium...

[Histoire romaine (latin). 1518-1533]

The so-called "Spanish model" - Tobacco industry strategies and its impact in Europe and Latin America

Background To demonstrate the tobacco industry rationale behind the "Spanish model" on non-smokers' protection in hospitality venues and the impact it had on some European and Latin American countries between 2006 and 2011. Methods Tobacco industry documents research triangulated against news and media reports. Results As an alternative to the successful implementation of 100% smoke-free policies, several European and Latin American countries introduced partial smoking bans based on the so-called "Spanish model", a legal framework widely advocated by parts of the hospitality industry with striking similarities to "accommodation programmes" promoted by the tobacco industry in the late 1990s. These developments started with the implementation of the Spanish tobacco control law (Ley 28/2005) in 2006 and have increased since then. Conclusion The Spanish experience demonstrates that partial smoking bans often resemble tobacco industry strategies and are used to spread a failed approach on international level. Researchers, advocates and policy makers should be aware of this ineffective policy.