title: Human TH17 cells express a functional IL-13 receptor and IL-13 attenuates IL-17A production.
abstract: BACKGROUND
  IL-13 is a central mediator of airway responsiveness and mucus expression in patients with allergic airway inflammation, and IL-13 is currently a therapeutic target for asthma. However, little is known about how IL-13 regulates human CD4(+) T-cell lineages because IL-13 receptor (IL-13R) α1, a subunit of IL-13R, has not previously been reported to exist on human T cells.
  
  
  OBJECTIVE
  We sought to determine whether human CD4(+) T(H)17 cells express IL-13Rα1 and whether IL-13 regulates T(H)17 cytokine production.
  
  
  METHODS
  Naive human CD4(+) cells were isolated from whole blood, activated with anti-CD3 and anti-CD28, and polarized to T(H)1, T(H)2, T(H)17, or induced regulatory T cells in the presence of IL-13 (0-10 ng/mL). Cell supernatants, total RNA, or total protein was examined 4 days after T(H)17 polarization.
  
  
  RESULTS
  T(H)17 cells, but not T(H)0, T(H)1, T(H)2, or induced regulatory T cells, expressed IL-13Rα1. IL-13 attenuated IL-17A production, as well as expression of retinoic acid-related orphan receptor, runt-related transcription factor-1, and interferon regulatory factor 4 in T(H)17-polarized cells. IL-13 neither inhibited IFN-γ production from T(H)1 cells nor inhibited IL-4 production from T(H)2 cells. Furthermore, attenuation of IL-17A production only occurred when IL-13 was present within 24 hours of T-cell activation or at the time of restimulation.
  
  
  CONCLUSIONS
  IL-13Rα1 is expressed on human CD4(+) T(H)17 cells, and IL-13 attenuates IL-17A production at polarization and restimulation. Although IL-13 is an attractive therapeutic target for decreasing symptoms associated with asthma, these results suggest that therapies inhibiting IL-13 production could have adverse side effects by increasing IL-17A production.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. dawn.newcomb@vanderbilt.edu
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Newcomb
authors.forename: Madison G
authors.initials: MG
authors.lastname: Boswell
authors.forename: Weisong
authors.initials: W
authors.lastname: Zhou
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Huckabee
authors.forename: Kasia
authors.initials: K
authors.lastname: Goleniewska
authors.forename: Carla M
authors.initials: CM
authors.lastname: Sevin
authors.forename: Gurjit K Khurana
authors.initials: GK
authors.lastname: Hershey
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
mesh_terms: D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism*; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000096:biosynthesis* / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D020381:Interleukin-17