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IL-25, a member of the IL-17 family of cytokines, is known to enhance type 2 immune responses, but suppress type 3 (IL-17A)-mediated immune responses. Mice deficient in IL-1 receptor antagonist (Il1rn−/− mice) have excessive IL-1 signaling, resulting in spontaneous development of IL-1–, TNF– and IL-17A–dependent aortitis. We found that expression of II25 mRNA was increased in the aortae of Il1rn−/− mice, suggesting that IL-25 may suppress development of IL-1–, TNF– and IL-17A–dependent aortitis in Il1rn−/− mice by inhibiting type 3-mediated immune responses. However, we unexpectedly found that Il25−/−Il1rn−/− mice showed attenuated development of aortitis, accompanied by reduced accumulation of inflammatory cells such as dendritic cells, macrophages and neutrophils and reduced mRNA expression of Il17a and Tnfa—but not Il4 or Il13—in local lesions compared with Il1rn−/− mice. Tissue–, but not immune cell–, derived IL-25 was crucial for development of aortitis. IL-25 enhanced IL-1β and TNF production by IL-25 receptor–expressing dendritic cells and macrophages, respectively, at inflammatory sites of aortae of Il1rn−/− mice, contributing to exacerbation of development of IL-1–, TNF– and IL-17A–dependent aortitis in those mice. Our findings suggest that neutralization of IL-25 may be a potential therapeutic target for aortitis.

The major downsides of cement manufacturing are the high CO2 emissions and high energy usage. Geopolymers, which are fabricated by activation of blends of fly ash (FA) and ground granulated blast furnace slag (GGBFS) using an alkaline activator, offer a promising solution to this issue. However, to enhance the replacement of cement in construction applications, geopolymer compositions have to be designed such that they can be activated on site by just adding water, similar to how cements are used. Therefore, the present work uses solid sodium metasilicate (MS, Na2SiO3) as the alkaline activator in order to design an add-water-style FA/GGBFS-based geopolymer composition. These compositions were designed by optimising the binder (FA/GGBFS) ratio, Na2SiO3/binder ratio, and water/binder ratio individually to assess the effects of these parameters on the setting times and mechanical (flexural and compressive) strengths over extended curing times (three months). The major factors affecting the strength development and setting times (initial and final) were the amounts of GGBFS and Na2SiO3, with the former demonstrating the more dominant effect. The consistent strength development with curing time was attributed to calcium aluminium silicate hydrate (CASH) gel formation in the early curing times which was affected by the slag addition levels, and sodium aluminium silicate hydrate (NASH) gel formation at later curing times which was influenced by the metasilicate addition levels. The metasilicate amounts were observed to impact on CASH gel formation in early stage curing. Geopolymer compositions with FA/GGBFS ratio of 35/65 and MS/water ratios of 0.2 showed high compressive strengths of ~70 MPa at 28 days, which are superior to values seen in conventional ordinary Portland cement (OPC) mixes for the same curing times.

Certain proteases derived from house dust mites and plants are considered to trigger initiation of allergic airway inflammation by disrupting tight junctions between epithelial cells. It is known that inhalation of proteases such as house dust mite-derived Der p1 and/or papaya-derived papain caused airway eosinophilia in naïve mice and even in Rag-deficient mice that lack acquired immune cells such as T, B and NKT cells. In contrast, little is known regarding the possible involvement of proteases derived from Aspergillus species (fungal-associated proteases; FAP), which are ubiquitous saprophytic fungi in the environment, in the development of allergic airway eosinophilia. Here, we found that inhalation of FAP by naïve mice led to airway eosinophilia that was dependent on protease-activated receptor-2 (PAR2), but not TLR2 and TLR4. Those findings suggest that the protease activity of FAP, but not endotoxins in FAP, are important in the setting. In addition, development of that eosinophilia was mediated by innate immune cells (ILCs) such as innate lymphoid cells, but not by acquired immune cells such as T, B and NKT cells. Whereas IL-33, IL-25 and thymic stromal lymphopoietin (TSLP) are involved in induction of FAP-induced ILC-mediated airway eosinophilia, IL-33—rather than IL-25 and/or TSLP—was critical for the eosinophilia in our model. Our findings improve our understanding of the molecular mechanisms involved in induction of airway inflammation by FAP.

IL-31, which is a member of the IL-6 family of cytokines, is produced mainly by activated CD4+ T cells, in particular activated Th2 cells, suggesting a contribution to development of type-2 immune responses. IL-31 was reported to be increased in specimens from patients with atopic dermatitis, and IL-31-transgenic mice develop atopic dermatitis-like skin inflammation, which is involved in the pathogenesis of atopic dermatitis. However, the role of IL-31 in development of contact dermatitis/contact hypersensitivity (CHS), which is mediated by hapten-specific T cells, including Th2 cells, is not fully understood. Therefore, we investigated this using IL-31-deficient (Il31−/−) mice, which we newly generated. We demonstrated that the mice showed normal migration and maturation of skin dendritic cells and induction of hapten-specific T cells in the sensitization phase of FITC-induced CHS, and normal induction of local inflammation in the elicitation phase of FITC- and DNFB-induced CHS. On the other hand, those mice showed reduced scratching frequency and duration during FITC- and/or DNFB-induced CHS. Our findings suggest that IL-31 is responsible for pruritus, but not induction of local skin inflammation, during CHS induced by FITC and DNFB.

Erythema dyschromicum perstans (EDP) and ashy dermatosis (AD) are pigmentary disorders of unknown etiology. EDP is usually considered to be identical to AD; however, a new clinical classification for EDP was proposed in the recent literature. Herein, we report a typical case of EDP observed in an African-American man. Interestingly, the late skin lesions in this case fit the criteria of AD as well. While there appear to be a few clinical cases that can be diagnosed as both EDP and AD based on the clinical course, the preponderance of the evidence in the published reports of EDP and AD and the clinical findings reported here strongly suggest that they are two distinct entities in terms of the extent of the inflammation, albeit on the same spectrum of pigment disorders.