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Modeling the HLH immune synapse uncovers critical roles for IS termination, cytokine intensity, and target cell death

A Frank-Kamenetskii, H Klinghoffer, J Varghese, V Dang, J Morrissette, JA Fraietta, C Diorio, JK Burkhardt, SW Canna

Blood 2025 PMID 40359482

- Commentary: HLH: it is all about communication

Canna lab on Google Scholar
Canna lab on PUBMED

1. Zhang M, Cron RR, Chu N, Nguyen J, Gordon SM, Eloseily EM, Atkinson TP, Weiser P, Walter MR, Kreiger PA, Canna SW, Behrens EM, Cron RQ. Role of DOCK8 in cytokine storm syndromes. The Journal of allergy and clinical immunology. 2025;155(3):1015-26 e5. Epub 20241017. doi: 10.1016/j.jaci.2024.10.004. PubMed PMID: 39423879; PMCID: PMC11875994.

2. Domblides C, Crampton S, Liu H, Bartleson JM, Nguyen A, Champagne C, Landy EE, Spiker L, Proffitt C, Bhattarai S, Grawe AP, Fuentealba Valenzuela M, Lartigue L, Mahouche I, Dupaul-Chicoine J, Nishimura K, Lefort F, Decraecker M, Velasco V, Netzer S, Pitard V, Roy C, Soubeyran I, Racine V, Blanco P, Dechanet-Merville J, Saleh M, Canna SW, Furman D, Faustin B. Human NLRC4 expression promotes cancer survival and associates with type I interferon signaling and immune infiltration. J Clin Invest. 2024;134(11). Epub 20240423. doi: 10.1172/JCI166085. PubMed PMID: 38652550; PMCID: PMC11142746.

3. Landy E, Varghese J, Dang V, Szymczak-Workman A, Kane LP, Canna SW. Complementary HLH susceptibility factors converge on CD8 T-cell hyperactivation. Blood Adv. 2023;7(22):6949-63. Epub 20230922. doi: 10.1182/bloodadvances.2023010502. PubMed PMID: 37738167; PMCID: PMC10690564.

4. Chen G, Deutsch GH, Schulert GS, Zheng H, Jang S, Trapnell B, Lee PY, Macaubas C, Ho K, Schneider C, Saper VE, de Jesus AA, Krasnow MA, Grom A, Goldbach-Mansky R, Khatri P, Mellins ED, Canna SW. Identification of Distinct Inflammatory Programs and Biomarkers in Systemic Juvenile Idiopathic Arthritis and Related Lung Disease by Serum Proteome Analysis. Arthritis & rheumatology. 2022;74(7):1271-83. Epub 20220531. doi: 10.1002/art.42099. PubMed PMID: 35189047; PMCID: PMC9246966.

5. Stone DL, Ombrello A, Arostegui JI, Schneider C, Dang V, de Jesus A, Girard-Guyonvarc'h C, Gabay C, Lee W, Chae JJ, Aksentijevich I, Goldbach-Mansky RT, Kastner DL, Canna SW. Excess Serum Interleukin-18 Distinguishes Patients With Pathogenic Mutations in PSTPIP1. Arthritis & rheumatology. 2022;74(2):353-7. Epub 20220103. doi: 10.1002/art.41976. PubMed PMID: 34492165; PMCID: PMC8855702.

6. Van Der Kraak LA, Schneider C, Dang V, Burr AHP, Weiss ES, Varghese JA, Yang L, Hand TW, Canna SW. Genetic and commensal induction of IL-18 drive intestinal epithelial MHCII via IFNgamma. Mucosal immunology. 2021;14(5):1100-12. Epub 20210608. doi: 10.1038/s41385-021-00419-1. PubMed PMID: 34103660; PMCID: PMC8562907.

8. Tsoukas P, Rapp E, Van Der Kraak L, Weiss ES, Dang V, Schneider C, Klein E, Picarsic J, Salcedo R, Stewart CA, Canna SW. Interleukin-18 and cytotoxic impairment are independent and synergistic causes of murine virus-induced hyperinflammation. Blood. 2020;136(19):2162-74. Epub 2020/06/27. doi: 10.1182/blood.2019003846. PubMed PMID: 32589707; PMCID: PMC7645987.

9. Canna SW, Girard C, Malle L, de Jesus A, Romberg N, Kelsen J, Surrey LF, Russo P, Sleight A, Schiffrin E, Gabay C, Goldbach-Mansky R, Behrens EM. Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition. The Journal of allergy and clinical immunology. 2017;139(5):1698-701. Epub 20161119. doi: 10.1016/j.jaci.2016.10.022. PubMed PMID: 27876626; PMCID: PMC5846100.

10. Canna SW, de Jesus AA, Gouni S, Brooks SR, Marrero B, Liu Y, DiMattia MA, Zaal KJ, Sanchez GA, Kim H, Chapelle D, Plass N, Huang Y, Villarino AV, Biancotto A, Fleisher TA, Duncan JA, O'Shea JJ, Benseler S, Grom A, Deng Z, Laxer RM, Goldbach-Mansky R. An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet. 2014;46(10):1140-6. Epub 2014/09/15. doi: 10.1038/ng.3089. PubMed PMID: 25217959; PMCID: PMC4177369.

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