@article {341,
	title = {Biallelic mutations in IRF8 impair human NK cell maturation and function.},
	journal = {J Clin Invest},
	volume = {127},
	year = {2017},
	month = {2017 01 03},
	pages = {306-320},
	abstract = {<p>Human NK cell deficiencies are rare yet result in severe and often fatal disease, particularly as a result of viral susceptibility. NK cells develop from hematopoietic stem cells, and few monogenic errors that specifically interrupt NK cell development have been reported. Here we have described biallelic mutations in IRF8, which encodes an interferon regulatory factor, as a cause of familial NK cell deficiency that results in fatal and severe viral disease. Compound heterozygous or homozygous mutations in IRF8 in 3 unrelated families resulted in a paucity of mature CD56dim NK cells and an increase in the frequency of the immature CD56bright NK cells, and this impairment in terminal maturation was also observed in Irf8-/-, but not Irf8+/-, mice. We then determined that impaired maturation was NK cell intrinsic, and gene expression analysis of human NK cell developmental subsets showed that multiple genes were dysregulated by IRF8 mutation. The phenotype was accompanied by deficient NK cell function and was stable over time. Together, these data indicate that human NK cells require IRF8 for development and functional maturation and that dysregulation of this function results in severe human disease, thereby emphasizing a critical role for NK cells in human antiviral defense.</p>},
	keywords = {Alleles, Animals, CD56 Antigen, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Humans, Interferon Regulatory Factors, Killer Cells, Natural, Male, Mice, Mice, Knockout, Mutation, Virus Diseases},
	issn = {1558-8238},
	doi = {10.1172/JCI86276},
	author = {Mace, Emily M and Bigley, Venetia and Gunesch, Justin T and Chinn, Ivan K and Angelo, Laura S and Care, Matthew A and Maisuria, Sheetal and Keller, Michael D and Togi, Sumihito and Watkin, Levi B and LaRosa, David F and Jhangiani, Shalini N and Muzny, Donna M and Stray-Pedersen, Asbj{\o}rg and Coban Akdemir, Zeynep and Smith, Jansen B and Hern{\'a}ndez-Sanabria, Mayra and Le, Duy T and Hogg, Graham D and Cao, Tram N and Freud, Aharon G and Szymanski, Eva P and Savic, Sinisa and Collin, Matthew and Cant, Andrew J and Gibbs, Richard A and Holland, Steven M and Caligiuri, Michael A and Ozato, Keiko and Paust, Silke and Doody, Gina M and Lupski, James R and Orange, Jordan S}
}
@article {173,
	title = {COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis.},
	journal = {Nat Genet},
	volume = {47},
	year = {2015},
	month = {2015 Jun},
	pages = {654-60},
	abstract = {<p>Unbiased genetic studies have uncovered surprising molecular mechanisms in human cellular immunity and autoimmunity. We performed whole-exome sequencing and targeted sequencing in five families with an apparent mendelian syndrome of autoimmunity characterized by high-titer autoantibodies, inflammatory arthritis and interstitial lung disease. We identified four unique deleterious variants in the COPA gene (encoding coatomer subunit α) affecting the same functional domain. Hypothesizing that mutant COPA leads to defective intracellular transport via coat protein complex I (COPI), we show that COPA variants impair binding to proteins targeted for retrograde Golgi-to-ER transport. Additionally, expression of mutant COPA results in ER stress and the upregulation of cytokines priming for a T helper type 17 (TH17) response. Patient-derived CD4(+) T cells also demonstrate significant skewing toward a TH17 phenotype that is implicated in autoimmunity. Our findings uncover an unexpected molecular link between a vesicular transport protein and a syndrome of autoimmunity manifested by lung and joint disease. </p>},
	keywords = {Amino Acid Sequence, Arthritis, Autoimmune Diseases, Child, Preschool, Coatomer Protein, Endoplasmic Reticulum, Endoplasmic Reticulum Stress, Female, Genetic Association Studies, Genetic Predisposition to Disease, Golgi Apparatus, HEK293 Cells, Humans, Infant, Lod Score, Lung Diseases, Interstitial, Male, Molecular Sequence Data, Pedigree, Protein Transport},
	issn = {1546-1718},
	doi = {10.1038/ng.3279},
	author = {Watkin, Levi B and Jessen, Birthe and Wiszniewski, Wojciech and Vece, Timothy J and Jan, Max and Sha, Youbao and Thamsen, Maike and Santos-Cortez, Regie L P and Lee, Kwanghyuk and Gambin, Tomasz and Forbes, Lisa R and Law, Christopher S and Stray-Pedersen, Asbj{\o}rg and Cheng, Mickie H and Mace, Emily M and Anderson, Mark S and Liu, Dongfang and Tang, Ling Fung and Nicholas, Sarah K and Nahmod, Karen and Makedonas, George and Canter, Debra L and Kwok, Pui-Yan and Hicks, John and Jones, Kirk D and Penney, Samantha and Jhangiani, Shalini N and Rosenblum, Michael D and Dell, Sharon D and Waterfield, Michael R and Papa, Feroz R and Muzny, Donna M and Zaitlen, Noah and Leal, Suzanne M and Gonzaga-Jauregui, Claudia and Boerwinkle, Eric and Eissa, N Tony and Gibbs, Richard A and Lupski, James R and Orange, Jordan S and Shum, Anthony K}
}
