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Browsing by Author "Craig, Maria E."
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Item IL-21 restricts T follicular regulatory T cell proliferation through Bcl-6 mediated inhibition of responsiveness to IL-2(Springer Nature, 2017-03-17) Jandl, Christoph; Liu, Sue M.; Cañete, Pablo F.; Warren, Joanna; Hughes, William E.; Vogelzang, Alexis; Webster, Kylie; Craig, Maria E.; Uzel, Gulbu; Dent, Alexander; Stepensky, Polina; Keller, Bärbel; Warnatz, Klaus; Sprent, Jonathan; King, Cecile; Microbiology and Immunology, School of MedicineT follicular regulatory (Tfr) cells control the magnitude and specificity of the germinal centre reaction, but how regulation is contained to ensure generation of high-affinity antibody is unknown. Here we show that this balance is maintained by the reciprocal influence of interleukin (IL)-2 and IL-21. The number of IL-2-dependent FoxP3+ regulatory T cells is increased in the peripheral blood of human patients with loss-of-function mutations in the IL-21 receptor (IL-21R). In mice, IL-21:IL-21R interactions influence the phenotype of T follicular cells, reducing the expression of CXCR4 and inhibiting the expansion of Tfr cells after T-cell-dependent immunization. The negative effect of IL-21 on Tfr cells in mice is cell intrinsic and associated with decreased expression of the high affinity IL-2 receptor (CD25). Bcl-6, expressed in abundance in Tfr cells, inhibits CD25 expression and IL-21-mediated inhibition of CD25 is Bcl-6 dependent. These findings identify a mechanism by which IL-21 reinforces humoral immunity by restricting Tfr cell proliferation.Item IL-6 receptor blockade does not slow β cell loss in new-onset type 1 diabetes(American Society for Clinical Investigation, 2021) Greenbaum, Carla J.; Serti, Elisavet; Lambert, Katharina; Weiner, Lia J.; Kanaparthi, Sai; Lord, Sandra; Gitelman, Stephen E.; Wilson, Darrell M.; Gaglia, Jason L.; Griffin, Kurt J.; Russell, William E.; Raskin, Philip; Moran, Antoinette; Willi, Steven M.; Tsalikian, Eva; DiMeglio, Linda A.; Herold, Kevan C.; Moore, Wayne V.; Goland, Robin; Harris, Mark; Craig, Maria E.; Schatz, Desmond A.; Baidal, David A.; Rodriguez, Henry; Utzschneider, Kristina M.; Nel, Hendrik J.; Soppe, Carol L.; Boyle, Karen D.; Cerosaletti, Karen; Keyes-Elstein, Lynette; Long, S. Alice; Thomas, Ranjeny; McNamara, James G.; Buckner, Jane H.; Sanda, Srinath; ITN058AI EXTEND Study Team; Pediatrics, School of MedicineBackground: IL-6 receptor (IL-6R) signaling drives development of T cell populations important to type 1 diabetes pathogenesis. We evaluated whether blockade of IL-6R with monoclonal antibody tocilizumab would slow loss of residual β cell function in newly diagnosed type 1 diabetes patients. Methods: We conducted a multicenter, randomized, placebo-controlled, double-blind trial with tocilizumab in new-onset type 1 diabetes. Participants were screened within 100 days of diagnosis. Eligible participants were randomized 2:1 to receive 7 monthly doses of tocilizumab or placebo. The primary outcome was the change from screening in the mean AUC of C-peptide collected during the first 2 hours of a mixed meal tolerance test at week 52 in pediatric participants (ages 6–17 years). Results: There was no statistical difference in the primary outcome between tocilizumab and placebo. Immunophenotyping showed reductions in downstream signaling of the IL-6R in T cells but no changes in CD4 memory subsets, Th17 cells, Tregs, or CD4+ T effector cell resistance to Treg suppression. A DC subset decreased during therapy but regressed to baseline once therapy stopped. Tocilizumab was well tolerated. Conclusion: Tocilizumab reduced T cell IL-6R signaling but did not modulate CD4+ T cell phenotypes or slow loss of residual β cell function in newly diagnosed individuals with type 1 diabetes.Item ISPAD Clinical Practice Consensus Guidelines 2018: Glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes(Wiley, 2018-10) DiMeglio, Linda A.; Acerini, Carlo L.; Codner, Ethel; Craig, Maria E.; Hofer, Sabine E.; Pillay, Kubendran; Maahs, David M.; Pediatrics, School of MedicineItem ISPAD Clinical Practice Consensus Guidelines 2022: Editorial(Wiley, 2022) Craig, Maria E.; Codner, Ethel; Mahmud, Farid H.; Marcovecchio, M. Loredana; DiMeglio, Linda A.; Priyambada, Leena; Wolfsdorf, Joseph I.; Pediatrics, School of MedicineItem ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes(Wiley, 2023) de Bock, Martin; Codner, Ethel; Craig, Maria E.; Huynh, Tony; Maahs, David M.; Mahmud, Farid H.; Marcovecchio, Loredana; DiMeglio, Linda A.; Pediatrics, School of MedicineItem ISPAD Clinical Practice Consensus Guidelines 2022: Management of cystic fibrosis-related diabetes in children and adolescents(Wiley, 2022) Larson Ode, Katie; Ballman, Manfred; Battezzati, Alberto; Brennan, Amanda; Chan, Christine L.; Hameed, Shihab; Ismail, Heba M.; Kelly, Andrea; Moran, Antoinette M.; Rabasa-Lhoret, Remi; Saxby, Nichole A.; Craig, Maria E.; Pediatrics, School of Medicine