Generation of two hiPSCs lines of two patients carrying truncating mutations in the dimerization domain of filamin C.

Here we introduce the human induced pluripotent stem cell lines (hiPSCs), HIMRi004-A and HIMRi005-A from dermal fibroblasts of a 48-year-old female (HIMRi004-A) carrying missense mutation that translate to the first described filamin C isoform p.W2710X and from a 56-year-old female (HIMRi005-A) carrying a recently described mutation in the same domain p.Y2704X. Both lines are generated via lentiviral expression of OCT4, SOX2, KLF4 and c-MYC. The lines display a typical embryonic stem cell-like morphology, express pluripotency markers, retain a normal karyotype (46, XX) and have the differentiation capacity in all three germ layers. The two lines can be used to elucidate the pathomechanisms of FLNC myofibrillar myopathies and to develop novel therapeutic options.

IL-1ß as mucosal vaccine adjuvant: the specific induction of tissue-resident memory T cells improves the heterosubtypic immunity against influenza A viruses.

A universal influenza vaccine must provide protection against antigenically divergent influenza viruses either through broadly neutralizing antibodies or cross-reactive T cells. Here, intranasal immunizations with recombinant adenoviral vectors (rAd) encoding hemagglutinin (HA) and nucleoprotein (NP) in combination with rAd-Interleukin-(IL)-1ß or rAd-IL-18 were evaluated for their efficacy in BALB/c mice. Mucosal delivery of rAd-IL-1ß enhanced HA-specific antibody responses including strain-specific neutralizing antibodies. Nevertheless, the beneficial effects on the local T cell responses were much more impressive reflected by increased numbers of CD103+CD69+ tissue-resident memory T cells (TRM). This increased immunogenicity translated into superior protection against infections with homologous and heterologous strains including H1N1, pH1N1, H3N2, and H7N7. Inhibition of the egress of circulating T cells out of the lymph nodes during the heterologous infection had no impact on the degree of protection underscoring the unique potential of TRM for the local containment of mucosal infections. The local co-expression of IL-1ß and antigen lead to the activation of critical checkpoints in the formation of TRM including activation of epithelial cells, expression of chemokines and adhesion molecules, recruitment of lung-derived CD103+ DCs, and finally local TRM imprinting. Given the importance of TRM-mediated protection at mucosal barriers, this study has major implications for vaccine development.