ArticleThe Journal of allergy and clinical immunology2016
Chediak-Higashi syndrome: Lysosomal trafficking regulator domains regulate exocytosis of lytic granules but not cytokine secretion by natural killer cells.
Article in The Journal of allergy and clinical immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 63 citations in OpenAlex.
- Single-nucleus RNA sequencing illuminates a functional analog of lymphoid organ in crustacean.Journal of advanced research · 2026Article
- Unraveling Lysosomal Exocytosis: From Molecular Mechanisms to Physiological Functions.Traffic (Copenhagen, Denmark) · 2026Review
- Genetic and molecular approaches for patients with familial hemophagocytic lymphohistiocytosis: a multi-center experience from Mexico.Frontiers in immunology · 2026Article
- Molecular diagnosis of inherited platelet disorders: a tale of two realities - advanced vs. resource-limited setting.Thrombosis journal · 2025Review
- Natural killer cells in skin: a unique opportunity to better characterize the many facets of an overlooked secondary lymphoid organ.Frontiers in immunology · 2025Review
- Spectrum ofJournal of medical genetics · 2024Review
- Unraveling the dynamic mechanisms of natural killer cells in viral infections: insights and implications.Virology journal · 2024Review
- Genetics of Primary Hemophagocytic Lymphohistiocytosis.Advances in experimental medicine and biology · 2024Review
- The lysosomal trafficking regulator "LYST": an 80-year traffic jam.Frontiers in immunology · 2024Review
- CD8Advances in experimental medicine and biology · 2024Review
- Comparative transcriptomes reveal pro-survival and cytotoxic programs of mucosal-associated invariant T cells upon Bacillus Calmette-Guérin stimulation.Frontiers in cellular and infection microbiology · 2023Article
- Comparative transcriptomics of porcine liver-resident CD8αFrontiers in immunology · 2023Article
- cDNA sequencing increases the molecular diagnostic yield in Chediak-Higashi syndrome.Frontiers in genetics · 2023Article
- The lysosomal trafficking regulator is necessary for normal wound healing.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2022Article
- Traffic jam within lymphocytes: A clinician's perspective.Frontiers in immunology · 2022Review
- Biology and pathology of the uterine microenvironment and its natural killer cells.Cellular & molecular immunology · 2021Review
- Germline and somatic mutations in the pathology of pineal cyst: A whole-exome sequencing study of 93 individuals.Molecular genetics & genomic medicine · 2021Article
- Mauve/LYST limits fusion of lysosome-related organelles and promotes centrosomal recruitment of microtubule nucleating proteins.Developmental cell · 2021Article
- Digenic Inheritance: Evidence and Gaps in Hemophagocytic Lymphohistiocytosis.Frontiers in immunology · 2021Review
- Filamin A Is Required for NK Cell Cytotoxicity at the Expense of Cytokine ProductionFrontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMutations in lysosomal trafficking regulator (LYST) cause Chediak-Higashi syndrome (CHS), a rare immunodeficiency with impaired cytotoxic lymphocyte function, mainly that of natural killer (NK) cells. Our understanding of NK cell function deficiency in patients with CHS and how LYST regulates lytic granule exocytosis is very limited.
objectiveWe sought to delineate cellular defects associated with LYST mutations responsible for the impaired NK cell function seen in patients with CHS.
methodsWe analyzed NK cells from patients with CHS with missense mutations in the LYST ARM/HEAT (armadillo/huntingtin, elongation factor 3, protein phosphatase 2A, and the yeast kinase TOR1) or BEACH (beige and Chediak-Higashi) domains.
resultsNK cells from patients with CHS displayed severely reduced cytotoxicity. Mutations in the ARM/HEAT domain led to a reduced number of perforin-containing granules, which were significantly increased in size but able to polarize to the immunologic synapse; however, they were unable to properly fuse with the plasma membrane. Mutations in the BEACH domain resulted in formation of normal or slightly enlarged granules that had markedly impaired polarization to the IS but could be exocytosed on reaching the immunologic synapse. Perforin-containing granules in NK cells from patients with CHS did not acquire certain lysosomal markers (lysosome-associated membrane protein 1/2) but were positive for markers of transport vesicles (cation-independent mannose 6-phosphate receptor), late endosomes (Ras-associated binding protein 27a), and, to some extent, early endosomes (early endosome antigen 1), indicating a lack of integrity in the endolysosomal compartments. NK cells from patients with CHS had normal cytokine compartments and cytokine secretion.
conclusionLYST is involved in regulation of multiple aspects of NK cell lytic activity, ranging from governance of lytic granule size to control of their polarization and exocytosis, as well as regulation of endolysosomal compartment identity. LYST functions in the regulated exocytosis but not in the constitutive secretion pathway.
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