Abbreviations used: CNS, central nervous system; EAE, experimental autoimmune encephalomyelitis; MBP, myelin basic protein; MS, multiple sclerosis; NS, nonsense. The extent to which myelin-specific Th1 and Th17 cells contribute to the pathogenesis of experimental autoimmune encephalomyelitis (EAE) is controversial. Combinations of interleukin (IL)-1, IL-6, and IL-23 with transforming growth factor  were used to differentiate myelin-specific T cell receptor transgenic T cells into Th17 cells, none of which could induce EAE, whereas Th1 cells consistently transferred disease. However, IL-6 was found to promote the differentiation of encephalitogenic Th17 cells. Further analysis of myelinspecific T cells that were encephalitogenic in spontaneous EAE and actively induced EAE demonstrated that T-bet expression was critical for pathogenicity, regardless of cytokine expression by the encephalitogenic T cells. These data suggest that encephalitogenicity of myelin-specific T cells appears to be mediated by a pathway dependent on T-bet and not necessarily pathway-specific end products, such as interferon  and IL-17. T-bet is

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have indeed shown greater mechanical performance than the traditional hydrogels. [8][9][10][11][12][13] However, problems still remained in terms of the applications of these hydrogels in biomedical fi elds. First, even if the elasticity of these hydrogels is improved signifi cantly, the modulus is far worse to meet the needs. Beyond that, poor biocompatibility as well as the possible toxicity of degradation product of these hydrogels poses a potential risk for the health of living beings. [ 6,7,14 ] Natural polymers, such as agarose, gelatin, hyaluronic acid and silk, possessing good biocompatibility, and the nontoxic degradation products, have received increasing interest in biomedical fi elds in the past decades. [ 15 ] Although these natural polymer based hydrogels have been extensively studied as the potential matrix for tissue engineering, the poor mechanical performance of the natural polymer based hydrogels is still a major limitation or a disadvantage for their medical applications. [ 16 ] Therefore, many methods were employed to improve the mechanical properties of the natural polymer based hydrogels. Chemical crosslinking was used as a facile routine approach to boost the mechanical properties of the natural polymer based hydrogels, but the safety of the chemical crosslinking reagent involved was a primary concern and the use of that might cause some unfavorable problems. [ 14 ] Besides chemical crosslinking, other efforts such as physical treatments [ 17,18 ] or mixing with other natural/synthetic polymers, [ 15,19 ] have been made to strengthen the natural polymer based hydrogels, yet the problem is still no closer to be solved.Among all natural polymers, Bombyx mori silk fi broin (SF) is one of the ideal candidates for biomedical applications due to it combining suffi cient mechanical performance, biocompatibility, and biodegradability. [20][21][22][23][24] Many approaches were employed to fabricate the physically crosslinked silk based hydrogels, such as sonication, vortex, addition of ethanol, and electrical fi eld. [25][26][27][28][29] However, most of the SF based hydrogels show poor mechanical performance which is a major stumbling block for applications. Recently, though a new covalently crosslinked SF based hydrogel with signifi cant elasticity was engineered via a kind of bio-crosslink reagent, i.e., HRP (horseradish peroxide), [ 7 ] it still could not escape the fate of poor mechanical properties in terms of the softness. Besides, the formation of the heterogeneous aggregates of crosslinking sites in the process of gelation can result in the poor optical properties Physically Crosslinked Biocompatible Silk-Fibroin-Based Hydrogels with High Mechanical PerformanceKunyuan Luo , Yuhong Yang , and Zhengzhong Shao * Developing hydrogel which combines superior mechanical performance and biocompatibility attracts researchers' attention in recent years. Here, a novel biocompatible hydrogel with excellent mechanical performance, comprised of regenerated silk fi broin (RSF) and hydroxypropyl methyl ce...

Our understanding of the pathophysiology of multiple sclerosis (MS) has evolved significantly over the past two decades as the fields of immunology and neurobiology provide new avenues of exploration into the cause and mechanism of the disease. It has been known for decades that T cells have different cytokine phenotypes, yet the cytokine phenotype of pathogenic T cells in MS is still an area of debate. In EAE, it appears that IFNγ and IL-17, produced by Th1 and Th17 cells respectively, are not the critical factor that determines T cell encephalitogenicity. However, there are molecules such as IL-23, T-bet and STAT4, that appear to be critical, yet it is unclear whether all these molecules contribute to a common, yet undefined pathway, or act in a synergistic manner which culminates in encephalitogenicity has still to be determined. Therefore, the focus of research on effector T cells in MS should focus on pathways upstream of the cytokines that define Th1 and Th17 cells, since downstream products, such as IFNγ and IL-17, probably are not critical determinants of whether an effector T cells is capable of trafficking to the CNS and inducing inflammatory demyelination.