Regulation and role of GM-CSF production by human T helper cells in health and inflammation
Immunology
Final Report Abstract
In sum, this project has revealed novel information on the differential regulation of signature cytokines. It has, in particular, challenged the previous concept of IL-17 and GM-CSF coregulation, which served as an explanation for Th17 cell pathogenicity. It revealed a distinct GM-CSF producing T helper cell subset and correlated the presence of GM-CSF producing T cells in the CNS with multiple sclerosis. At the same time, it revealed a non-inflammatory homeostatic role for GM-CSF producing T cells in the human skin and thus tissue specific functional roles for GM-CSF producing T helper cells. Novel technologies of the ex vivo interrogation of the antigen specific repertoire of GM-CSF producing T cells, which have been established in the lab, will further reveal their specific role in human health and disease.
Publications
- (2014). Defining Th‐cell subsets in a classical and tissue‐specific manner: Examples from the skin. Eur J Immunol 44 (12), 3475-3483
Eyerich S, Zielinski, C.E.
(See online at https://doi.org/10.1002/eji.201444891) - (2014). IL-17 and GM-CSF Expression Are Antagonistically Regulated by Human T Helper Cells. Sci Transl Med 6, 241ra280
Noster R, Riedel R, Mashreghi MF, Radbruch H, Harms L, Haftmann C, Chang HD, Radbruch A, Zielinski CE
(See online at https://doi.org/10.1126/scitranslmed.3008706) - (2014). In vitro generation of microbe specific human Th17 cells. Methods Mol Biol. 1193:97-104
Braun J, Zielinski CE
(See online at https://doi.org/10.1007/978-1-4939-1212-4_10) - (2014). Microbe driven T-helper cell differentiation: lessons from Candida albicans and Staphylococcus aureus. Exp Dermatol. 23(11):795-8
Zielinski CE
(See online at https://doi.org/10.1111/exd.12493) - Autoimmunity beyond Th17: GM-CSF producing T cells. Cell Cycle 13, 2489-2490
Zielinski, CE
(See online at https://doi.org/10.4161/15384101.2014.946377) - (2016). Dysregulation of pro- versus anti-inflammatory human Th17 cell functionalities in the autoinflammatory Schnitzler syndrome. J Allergy Clin Immunol 138(4):1161-1169
Noster R, de Koning, HD, Maier E, Prelog M, Lainka E, Zielinski CE
(See online at https://doi.org/10.1016/j.jaci.2015.12.1338) - (2016). Epstein-Barr viral miRNAs inhibit antiviral CD4+ T cell responses targeting IL-12 and peptide processing. J Exp Med. 19;213(10):2065-80
Tagawa T, Albanese M, Bouvet M, Moosmann A, Mautner J, Heissmeyer V, Zielinski C, Lutter D, Hoser J, Hastreiter M, Hayes M, Sugden B, Hammerschmidt W
(See online at https://doi.org/10.1084/jem.20160248) - (2017). Hierarchical governance of cytokine production by 6‐sulfo Lac NA c (slan) dendritic cells for the control of psoriasis pathogenesis. Exp Dermatol. 26 (4), 317-318
Poltorak MP, Zielinski CE
(See online at https://doi.org/10.1111/exd.13170) - (2017). Human T cell immune surveillance: phenotypic, functional and migratory heterogeneity for tailored immune responses. Immunol letters 190, 125-129
Zielinski CE
(See online at https://doi.org/10.1016/j.imlet.2017.08.001) - (2017). Long-term response to gluten-free diet as evidence for non-celiac wheat sensitivity in one third of patients with diarrhea-dominant and mixed-type irritable bowel syndrome. Int J Colorectal Dis 32 (1), 29-39
Barmeyer C, Schumann M, Meyer T, Zielinski C, Zuberbier T, Siegmund B
(See online at https://doi.org/10.1007/s00384-016-2663-x) - (2017). TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestine. Mucosal Immunol. 10(6):1431-1442
Pascual-Reguant A, Bayat Sarmadi J, Baumann C, Noster R, Cirera-Salinas D, Curato C, Pelczar P, Huber S, Zielinski CE, Löhning M, Hauser AE, Esplugues E
(See online at https://doi.org/10.1038/mi.2017.5)