Systemic sclerosis (SSc) is a chronic multisystem disorder characterized by fibrosis and autoimmunity. Interleukin (IL)-31 has been implicated in fibrosis and T helper (Th) 2 immune responses, both of which are characteristics of SSc. The exact role of IL-31 in SSc pathogenesis is unclear. Here we show the overexpression of IL-31 and IL-31 receptor A (IL-31RA) in dermal fibroblasts (DFs) from SSc patients. We elucidate the dual role of IL-31 in SSc, where IL-31 directly promotes collagen production in DFs and indirectly enhances Th2 immune responses by increasing pro-Th2 cytokine expression in DFs. Furthermore, blockade of IL-31 with anti-IL-31RA antibody significantly ameliorates fibrosis and Th2 polarization in a mouse model of SSc. Therefore, in addition to defining IL-31 as a mediator of fibrosis and Th2 immune responses in SSc, our study provides a rationale for targeting the IL-31/IL-31RA axis in the treatment of SSc.

Analysis of a countable number of protein molecules released from living single cells was realized by a micro/nanofluidic device entirely integrating cellular processing and molecular processing into pL-microchannels and fL-nanochannels, respectively.

The extended-nanospace, a space on the scale of 10¹–10³ nm, is mostly unexplored due to the lack of sufficient experimental technology. Recently, the research of liquid properties in the extended-nanospace has gathered much interest, because the behavior of water molecules in this space is between that of liquid-like bulk phase water molecules and single molecules. Due to the large surface-to-volume ratio in the channel, the surface charge of the wall directly affects the water structure and ion distribution. The streaming potential/current measurement method, which is used to evaluate surface states directly, is an important and useful method to investigate the liquid properties. In this paper, we report a new method for measuring the streaming potential/current in size-controlled 2D extended-nanospace on glass substrate. Nano-in-microfluidic systems were fabricated on fused-silica glass substrates, and the liquid was air-driven using a pressure controller. An equivalent circuit of the detection system was designed to selectively detect the potential and current in the extended-nanospace. The basic measurement principle was verified using several different experiments. The absolute values obtained for the potential and current were also compared with the theoretical values for various channel sizes (360–1650 nm), and good agreement was observed for micrometre-scale channels. This technique will be valuable for the investigation of chemistry and fluidics in the extended-nanospace.

Nanofluidics have recently attracted significant attention with regard to the development of new functionalities and applications, and producing new functional devices utilizing nanofluidics will require the fabrication of nanochannels. Fused silica nanofluidic devices fabricated by top-down methods are a promising approach to realizing this goal. Our group previously demonstrated the analysis of a living single cell using such a device, incorporating nanochannels having different sizes (10²–10³ nm) and with branched and confluent structures and surface patterning. However, fabrication of geometrically-controlled nanochannels on the 10¹ nm size scale by top-down methods on a fused silica substrate, and the fabrication of micro-nano interfaces on a single substrate, remain challenging. In the present study, the smallest-ever square nanochannels (with a size of 50 nm) were fabricated on fused silica substrates by optimizing the electron beam exposure time, and the absence of channel breaks was confirmed by streaming current measurements. In addition, micro-nano interfaces between 10³ nm nanochannels and 10¹ μm microchannels were fabricated on a single substrate by controlling the hydrophobicity of the nanochannel surfaces. A micro-nano interface for a single cell analysis device, in which a nanochannel was connected to a 10¹ μm single cell chamber, was also fabricated. These new fabrication procedures are expected to advance the basic technologies employed in the field of nanofluidics.