Anti-TNF-alpha therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-beta

The induction of regulatory T (T reg) cells holds considerable potential as a treatment for autoimmune diseases. We have previously shown that CD4(+)CD25(hi) T reg cells isolated from patients with active rheumatoid arthritis (RA) have a defect in their ability to suppress proinflammatory cytokine production by CD4(+)CD25(-) T cells. This defect, however, was overcome after anti-tumor necrosis factor (TNF)-alpha antibody (infliximab) therapy. Here, we demonstrate that infliximab therapy gives rise to a CD4(+)CD25(hi)FoxP3(+) T reg cell population, which mediates suppression via transforming growth factor (TGF)-beta and interleukin 10, and lacks CD62L expression, thereby distinguishing this T reg cell subset from natural T reg cells present in healthy individuals and patients with active RA. In vitro, infliximab induced the differentiation of CD62L(-) T reg cells from CD4(+)CD25(-) T cells isolated from active RA patients, a process dependent on TGF-alpha. In spite of the potent suppressor capacity displayed by this CD62L(-) T reg cell population, the natural CD62L(+) T reg cells remained defective in infliximab-treated patients. These results suggest that anti-TNF-alpha therapy in RA patients generates a newly differentiated population of T reg cells, which compensates for the defective natural T reg cells. Therefore, manipulation of a proinflammatory environment could represent a therapeutic strategy for the induction of T reg cells and the restoration of tolerance

Prevention of arthritis by interleukin 10-producing B cells

In this study we have shown that activation of arthritogenic splenocytes with antigen and agonistic anti-CD40 gives raise to a B cell population that produce high levels of interleukin (IL)-10 and low levels of interferon (IFN)-{gamma}. Transfer of these B cells into DBA/1-TcR-ß-Tg mice, immunized with bovine collagen (CII) emulsified in complete Freund's adjuvant inhibited T helper type 1 differentiation, prevented arthritis development, and was also effective in ameliorating established disease. IL-10 is essential for the regulatory function of this subset of B cells, as the B cells population isolated from IL-10 knockout mice failed to mediate this protective function. Furthermore, B cells isolated from arthritogenic splenocytes treated in vitro with anti–IL-10/anti–IL-10R were unable to protect recipient mice from developing arthritis. Our results suggest a new role of a subset of B cells in controlling T cell differentiation and autoimmune disorders

Electron Transport and Hot Phonons in Carbon Nanotubes

We demonstrate the key role of phonon occupation in limiting the high-field ballistic transport in metallic carbon nanotubes. In particular, we provide a simple analytic formula for the electron transport scattering length, that we validate by accurate first principles calculations on (6,6) and (11,11) nanotubes. The comparison of our results with the scattering lengths fitted from experimental I-V curves indicates the presence of a non-equilibrium optical phonon heating induced by electron transport. We predict an effective temperature for optical phonons of thousands Kelvin.Comment: 4 pages, 1 figur

A clinical update on the significance of the gut microbiota in systemic autoimmunity

Systemic lupus erythematosus (SLE) is a complex autoimmune disease where a loss of tolerance to nuclear antigens leads to inflammation in multiple organ systems. The cause of SLE remains ill defined, although it is known that a complex interplay between genes and environment is necessary for disease development. In recent years, case studies have reported that the incidence of SLE in the USA, for example, has increased by approximately 3 fold. Although the reason for this is likely to be multifactorial, it has been hypothesized that the increasing incidence of autoimmune disease is due to considerable shifts in the bacterial communities resident the gut, collectively known as the gut microbiota, following a change in diet and the widespread introduction of antibiotics. Furthermore, a growing body of evidence suggests that the gut microbiota plays a role in the development of a range of autoimmune diseases including inflammatory bowel disease, multiple sclerosis, type one diabetes and rheumatoid arthritis. In this review, we summarize how advances in DNA-based sequencing technologies have been critical in providing baseline information concerning the gut microbiota in health and how variation amongst individuals in controlled by multiples factors including age, genetics, environment and the diet. We also discuss the importance of the gut microbiota in the development of a healthy immune system and how changes in particular bacterial phyla have been associated with immune abnormalities in animal models of autoimmune disease. Finally, in order to place the data in a clinical context, we highlight recent findings showing that abnormalities in the gut microbiota can be detected in patients with SLE, which provides the rationale for greater investigation into whether microbiota-targeted therapies could be used for the treatment/prevention of disease

Influence of the façades convective heat transfer coefficients on the thermal energy demand for an urban street canyon building

In an urban micro-climate environment, the convective heat transfer coefficient (CHTC) on the façades influences simulated building's energy demand and exterior wall surfaces temperatures. In this paper, it is analyzed how the CHTC values on the façades of a building located in an urban canyon influence the façades temperatures and how important is the choice of an accurate CHTC correlation on the space cooling and heating energy demand. CHTC correlations found in literature are based on some specific micro-climate parameters such as local wind speed, district construction density, temperature differences between façades and canyon air and wind direction. An accurate choice of the right correlation for the simulated urban environment is important to better represent the exterior walls heat removal due to outside wind climate. The effects of the use of different CHTC correlations have been evaluated by means of TRNSYS 17.0 simulation program. The study is performed for a building sited an urban street canyon with the aspect ratio H/W=1 and located in a Mediterranean climate, in Rome. The comparison performed between the results of the numerical simulations shows that some correlations lead to an underestimation of the space heating demand around 9.7% and to an overestimation of the space cooling demand around 17.5%

The emerging field of regulatory B cell immunometabolism

B cells are well known as critical mediators of humoral immune responses via the production of antibodies. However, numerous studies have also identified populations of B cells that are characterized by their anti-inflammatory properties. These “regulatory B cells” restrain excessive inflammatory responses in a wide range of health conditions. A significant knowledge gap remains concerning the nature of the signals that determine whether a B cell exerts a pro-inflammatory or anti-inflammatory function. In this perspective, we explore the concept that in addition to the cytokine microenvironment, intracellular and extracellular metabolic signals play a pivotal role in controlling the balance between regulatory and antibody-producing B cell subsets. Determining the metabolites and tissue-specific signals that influence B cell fate could establish novel therapeutic targets for the treatment of diseases where abnormal B cell responses contribute to pathogenesis