title: Differentiation and functional analysis of human T(H)17 cells.
abstract: BACKGROUND
  T(H)17 cells are of pathologic relevance in autoimmune disorders and presumably also in allergy and asthma. Regulatory T (Treg) cells, in contrast, suppress inflammatory and allergen-driven responses. Despite these disparate functions, both T-cell subsets have been shown to be dependent on TGF-beta for their development.
  
  
  OBJECTIVE
  The aim of the study was to analyze the differentiation and function of human T(H)17 cells in comparison with other T(H) cell subsets.
  
  
  METHODS
  Naive human CD4(+) T cells were differentiated in vitro, and gene expression was analyzed by means of quantitative real-time PCR, ELISA, and immunofluorescence. The function of T(H) cell subsets was assessed by monitoring the response of primary bronchial epithelial cells in coculture experiments.
  
  
  RESULTS
  In vitro differentiated T(H)17 cells differ from Treg and other T(H) cells in their potency to induce IL-6 and IL-1beta expression in primary bronchial epithelial cells. TGF-beta, IL-1beta, IL-6, and IL-23 are necessary during T(H)17 cell differentiation to acquire these functions, including IL-17 production. In contrast, TGF-beta alone is necessary and sufficient to induce the transcription factor RORC2. This transcription factor, previously thought to be specific for T(H)17 cells, is also expressed in Treg cells, CD25(+) cells, cytotoxic T cells, and natural killer T cells.
  
  
  CONCLUSIONS
  This study demonstrates mechanisms of differentiation to human T(H)17 cells, a subset that effectively and uniquely modulates the function of primary bronchial epithelial cells.
authors.affiliation: Swiss Institute for Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
authors.forename: Simone
authors.initials: S
authors.lastname: Burgler
authors.forename: Nadia
authors.initials: N
authors.lastname: Ouaked
authors.forename: Claudio
authors.initials: C
authors.lastname: Bassin
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Basinski
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Mantel
authors.forename: Kerstin
authors.initials: K
authors.lastname: Siegmund
authors.forename: Norbert
authors.initials: N
authors.lastname: Meyer
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
authors.forename: Carsten B
authors.initials: CB
authors.lastname: Schmidt-Weber
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology / Q000502:physiology*; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid / Q000276:immunology* / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D015850:Interleukin-6; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D016212:Transforming Growth Factor beta