Person: Poli Harlowe, María Cecilia
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Poli Harlowe
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María Cecilia
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María Cecilia Poli Harlowe
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Publication Multiomics dissection of human RAG deficiency revealsdistinctive patterns of immune dysregulation but acommon inflammatory signature(2025) Bosticardo, Marita; Dobbs, Kerry; Delmonte, Ottavia; Martins, Andrew; Pala, Francesca; Kawai, Tomoki; Kenney, Heather; Magro, Gloria; Rosen, Lindsey; Yamazaki, Yasuhiro; Yu, Hsin-Hui; Calzoni, Enrica; Lee, Yu Nee; Liu, Can; Stoddard, Jennifer; Niemela, Julie; Fink, Danielle; Castagnoli, Riccardo; Ramba, Meredith; Cheng, Aristine; Riley, Deanna; Oikonomou, Vasileios; Shaw, Elana; Belaid, Brahim; Keles, Sevgi; Al- Herz, Waleed; Cancrin, Caterina; Cifald, Cristina; Baris, Safa; Sharapova, Svetlana; Schuetz, Catharina; Gennery, Andrew; Freeman, Alexandra; Somech, Raz; Choo, Sharon; Giliani, Silvia; Güngör, Tayfun; Drozdov, Daniel; Meyt, Isabelle; Moshous, Despina; Neven, Benedicte; Abraham, Roshini; El- Marsafy, Aisha; Kanariou, Maria; King, Alejandra; Licciardi, Francesco; Cruz, Mario; Palma, Paolo; Poli Harlowe, María Cecilia; Adelo, Mehdi; Algeri, Mattia; Alroqi, Fayhan; Bastard, Paul; Bergerson, Jenna; Booth, Claire; Brett, Ana; Burns, Siobhan; Butt, Manish; Padem, Nurcicek; de la Morena, M. TeresaCompeting interests: M.J.B. is a speaker for Grifols; consults for Pharming, Horizon/Amgen, and Grifols; receives sponsored research funding from the NIH, the Bill and Melinda Gates Foundation, and Pharming; and serves on the scientific advisory board for ADMA Biologics. H.C.S. has stock holdings in Amgen and Eli Lily. R.S.A. receives royalties from Elsevier for book publications, serves as deputy editor for the Journal of Immunology, is Committee Chair of Newborn Screening for SCID for the Clinical and Laboratory Standards Institute, and is a member of the Immunology Clinical Domain Working Group for ClinGen. B.J.D.S. is an ad hoc consultant for Sobi and a member of the Data Safety Monitoring Board for Orchard Therapeutics. I.M. is a senior Clinical Researcher at the FWO Flanders. R.L.F. has consulted for Takeda, Griffons, Horizon, and Pharming. B.W. serves as consultant for the Immunology Speakers Bureau, Takeda Pharmaceutocals. S. Prockop receives support for the conduct of clinical trials through Boston Children’s Hospital from AlloVir, Atara, and Jasper. She is an inventor of intellectual property related to development of third-party virus-specific T cells program with all rights assigned to Memorial Sloan Kettering Cancer Center; receives honoraria from Pierre Fabre, Regeneron; serves on the data safety monitoring board at Stanford University and New York Blood Center; and is consulting for Atara, Ensoma, Pierre Fabre, HEOR and VOR. J.S.T. serves on the scientific advisory board of CytoReason Inc. and Immunoscape Inc. and as the co–chief science officer (unpaid) of the Human Immunome Project (nonprofit). All other authors declare that they have no competing interests.Publication TGFβ links EBV to multisystem inflammatory syndrome in children(2025) Goetzke, Carl; Massou, Mona; Frischbutt, Stefan; Guerra, Gabriela; Ferreira, Marta; Heinrich, Frederik; Von Stuckra, Anne; Wisniewsk, Sebastian; Lich, Jan; Bondarev, Marina; Ehler, Lisa; Khaldi, Samira; Javouhe, Etienne; Pons, Sylvie; Trouillet, Sophie; Ozsurek, Yasemin; Zhang, Yu; Poli Harlowe, María Cecilia; Discepolo, Valentina; Lo Vecchio, Andrea; Sahin, Bengü; Verboom, Murielle; Hallenslebe, Michael; Heuhse, Anja; Astudillo, Camila; Espinosa, Yazmin; Vial, Maria Cecilia; Dobbs, Kerry; Delmont, Ottavia; Montealegre, Gina; Magliocco, Mary; Barron, Karyl; Danielson, Jeffrey; Petrov, Lev; Unterwalder, Nadine; Sawitzk,i Birgit; Matz, Mareen; Lehmann, Katrin; Gratop, Alexander; Von Bernuth, Horst; Burkhardt, Lisa; Wiese, Niklas; Peter, Lena; Schmueck, Michael; Amini, Leila; Maurer, Marcus; Roehmel, Jobst; Gewur, Benjamin; Yonker, Lael; Witkowsk, Mario; Kruglov, Andrey; Mall, Marcus; Su, Helen; Ozen, Seza; Radbruch, Andreas; Belot, Alexandre; Durek, Pawel; Kallinich, Tilmann; Mashregh, Mir-FarzinIn a subset of children and adolescents, SARS-CoV-2 infection induces a severe acute hyperinflammatory shock1 termed multisystem inflammatory syndrome in children (MIS-C) at four to eight weeks after infection. MIS-C is characterized by a specific T cell expansion2 and systemic hyperinflammation3. The pathogenesis of MIS-C remains largely unknown. Here we show that acute MIS-C is characterized by impaired reactivation of virus-reactive memory T cells, which depends on increased serum levels of the cytokine TGFβ resembling those that occur during severe COVID-19 (refs. 4,5). This functional impairment in T cell reactivity is accompanied by the presence of TGFβ-response signatures in T cells, B cells and monocytes along with reduced antigen-presentation capabilities of monocytes, and can be reversed by blocking TGFβ. Furthermore, T cell receptor repertoires of patients with MIS-C exhibit expansion of T cells expressing TCRVβ21.3, resembling Epstein-Barr virus (EBV)-reactive T cell clones capable of eliminating EBV-infected B cells. Additionally, serum TGFβ in patients with MIS-C can trigger EBV reactivation, which is reversible with TGFβ blockade. Clinically, the TGFβ-induced defect in T cell reactivity correlates with a higher EBV seroprevalence in patients with MIS-C compared with age-matched controls, along with the occurrence of EBV reactivation. Our findings establish a connection between SARS-CoV-2 infection and COVID-19 sequelae in children, in which impaired T cell cytotoxicity triggered by TGFβ overproduction leads to EBV reactivation and subsequent hyperinflammation.