Regulation and role of GM-CSF production by human T helper cells in health and inflammation

• Applicant: Professorin Dr. Christina Zielinski
• Subject Area: Dermatology ; Immunology
• Term: from 2013 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 233380263

• Final Report Year: 2018

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.
  
• (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
  
• (2014). In vitro generation of microbe specific human Th17 cells. Methods Mol Biol. 1193:97-104
  Braun J, Zielinski CE
  
• (2014). Microbe driven T-helper cell differentiation: lessons from Candida albicans and Staphylococcus aureus. Exp Dermatol. 23(11):795-8
  Zielinski CE
  
• Autoimmunity beyond Th17: GM-CSF producing T cells. Cell Cycle 13, 2489-2490
  Zielinski, CE
  
• (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
  
• (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
  
• (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
  
• (2017). Human T cell immune surveillance: phenotypic, functional and migratory heterogeneity for tailored immune responses. Immunol letters 190, 125-129
  Zielinski CE
  
• (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
  
• (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