Tuning T helper cell differentiation by ITK.

CD4+ effector T cells effectuate T cell immune responses, producing cytokines to orchestrate the nature and type of immune responses. The non-receptor tyrosine kinase IL-2 inducible T cell kinase (ITK), a mediator of T cell Receptor signaling, plays a critical role in tuning the development of these effector cells. In this review we discussed the role that signals downstream of ITK, including the Ras/MAPK pathway, play in differentially controlling the differentiation of TH17, Foxp3+ T regulatory (Treg) cells, and Type 1 regulatory T (Tr1) cells, supporting a model of ITK signals controlling a decision point in the effector T cell differentiation process.

Interleukin-2-Inducible T-Cell Kinase Deficiency Impairs Early Pulmonary Protection Against Infection.

Interleukin-2 (IL-2) inducible T-cell kinase (ITK) is a non-receptor tyrosine kinase highly expressed in T-cell lineages and regulates multiple aspects of T-cell development and function, mainly through its function downstream of the T-cell receptor. deficiency can lead to CD4 lymphopenia and Epstein-Bar virus (EBV)-associated lymphoproliferation and recurrent pulmonary infections in humans. However, the role of the ITK signaling pathway in pulmonary responses in active tuberculosis due to infection is not known.

Adeno-associated viral vector-mediated immune responses: Understanding barriers to gene delivery.

Adeno-associated viral (AAV) vectors have emerged as the leading gene delivery platform for gene therapy and vaccination. Three AAV-based gene therapy drugs, Glybera, LUXTURNA, and ZOLGENSMA were approved between 2012 and 2019 by the European Medicines Agency and the United States Food and Drug Administration as treatments for genetic diseases hereditary lipoprotein lipase deficiency (LPLD), inherited retinal disease (IRD), and spinal muscular atrophy (SMA), respectively. Despite these therapeutic successes, clinical trials have demonstrated that host anti-viral immune responses can prevent the long-term gene expression of AAV vector-encoded genes.

Inhibition of type I interferon responses by adenovirus serotype-dependent Gas6 binding.

The clinical use of many adenovirus vaccine vectors (AdVs) is limited by the presence of pre-existing antibodies in human populations, which prevent common AdVs from transducing cells and expressing immunogenic gene products. Rare serotype AdVs, such as HAdV-28D can bypass pre-existing immunity. However, rare AdVs stimulate high-levels of type I interferon (IFN), which suppresses antigenic gene expression and therefore limits immunogenicity.