Treating primary immunodeficiencies with defects in NK cells: from stem cell therapy to gene editing
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(2020) 11:453
REVIEW
Open Access
Treating primary immunodeficiencies with defects in NK cells: from stem cell therapy to gene editing C. Eguizabal1,2*, L. Herrera1,2, M. Inglés-Ferrándiz1,2 and J. C. Izpisua Belmonte3
Abstract Primary immunodeficiency diseases (PIDs) are rare diseases that are characterized by genetic mutations that damage immunological function, defense, or both. Some of these rare diseases are caused by aberrations in the normal development of natural killer cells (NKs) or affect their lytic synapse. The pathogenesis of these types of diseases as well as the processes underlying target recognition by human NK cells is not well understood. Utilizing induced pluripotent stem cells (iPSCs) will aid in the study of human disorders, especially in the PIDs with defects in NK cells for PID disease modeling. This, together with genome editing technology, makes it possible for us to facilitate the discovery of future therapeutics and/or cell therapy treatments for these patients, because, to date, the only curative treatment available in the most severe cases is hematopoietic stem cell transplantation (HSCT). Recent progress in gene editing technology using CRISPR/Cas9 has significantly increased our capability to precisely modify target sites in the human genome. Among the many tools available for us to study human PIDs, disease- and patient-specific iPSCs together with gene editing offer unique and exceptional methodologies to gain deeper and more thorough understanding of these diseases as well as develop possible alternative treatment strategies. In this review, we will discuss some immunodeficiency disorders affecting NK cell function, such as classical NK deficiencies (CNKD), functional NK deficiencies (FNKD), and PIDs with involving NK cells as well as strategies to model and correct these diseases for further study and possible avenues for future therapies. Keywords: Primary immunodeficiency diseases (PIDs), Induced pluripotent stem cells (iPSCs), Gene editing, CRISPRCas9, Stem cell therapy, Hematopoietic stem cells, Natural killer cells
Background Primary immunodeficiency disorders (PIDs) are rare diseases caused by genetic mutations that damage immunological function, defense, or both. PIDs refer to over 130 disorders that result from developmental and/or functional defects in one or more cell types of the immune system. PIDs are generally classified as disorders of adaptive immunity (B cell, T cell, or combined * Correspondence: [email protected] 1 Cell Therapy, Stem Cells and Tissues Group, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain 2 Research Unit, Basque Center for Blood Transfusion and Human Tissues, Osakidetza, Galdakao, Spain Full list of author information is available at the end of the article
immunodeficiencies) or innate immunity (NK cells, phagocyte, and complement disorders). Some of these diseases affect natural killer (NK) cells [1, 2]. NK cells are lymphocytes of the innate immune system poised to deliver a response immediately after
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