Patients with cystic fibrosis have inducible IL-17+IL-22+ memory cells in lung draining lymph nodes - 30/03/13
, Kong Chen, PhD b, Steven R. Duncan, MD a, Kira L. Lathrop, MAMS c, Joseph D. Latoche, BS a, Alison J. Logar, BS b, Derek A. Pociask, PhD b, Brendon J. Wahlberg, MS a, Prabir Ray, PhD a, Anuradha Ray, PhD a, Joseph M. Pilewski, MD a, Jay K. Kolls, MD b
Corresponding author: Yvonne R. Chan, MD, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, 3459 Fifth Avenue, NW 628 MUH, Pittsburgh, PA 15213.Abstract |
Background |
IL-17 is an important cytokine signature of the TH differentiation pathway TH17. This T-cell subset is crucial in mediating autoimmune disease or antimicrobial immunity in animal models, but its presence and role in human disease remain to be completely characterized.
Objective |
We set out to determine the frequency of TH17 cells in patients with cystic fibrosis (CF), a disease in which there is recurrent infection with known pathogens.
Methods |
Explanted lungs from patients undergoing transplantation or organ donors (CF samples = 18; non-CF, nonbronchiectatic samples = 10) were collected. Hilar nodes and parenchymal lung tissue were processed and examined for TH17 signature by using immunofluorescence and quantitative real-time PCR. T cells were isolated and stimulated with antigens from Pseudomonas aeruginosa and Aspergillus species. Cytokine profiles and staining with flow cytometry were used to assess the reactivity of these cells to antigen stimulation.
Results |
We found a strong IL-17 phenotype in patients with CF compared with that seen in control subjects without CF. Within this tissue, we found pathogenic antigen–responsive CD4+IL-17+ cells. There were double-positive IL-17+IL-22+ cells [TH17(22)], and the IL-22+ population had a higher proportion of memory characteristics. Antigen-specific TH17 responses were stronger in the draining lymph nodes compared with those seen in matched parenchymal lungs.
Conclusion |
Inducible proliferation of TH17(22) with memory cell characteristics is seen in the lungs of patients with CF. The function of these individual subpopulations will require further study regarding their development. T cells are likely not the exclusive producers of IL-17 and IL-22, and this will require further characterization.
Le texte complet de cet article est disponible en PDF.Key words : TH17, TH22, IL-17, IL-22, cystic fibrosis, Pseudomonas species, Aspergillus species, chronic infectious disease, memory T-cell response, lung transplant
Abbreviations used : Asp, CF, Con A, COPD, CORE, DLN, NK, Pa(EL), Pa(LL), PLC, ROR, TCR
Plan
| Supported by research grants from the National Heart, Lung, and Blood Institute, National Institutes of Health (K08 HL089189 to Y.R.C. and P50 HL084932 to J.K.K. and J.M.P.), the Howard Hughes Medical Institute (Early Career Physician Scientist Award to Y.R.C.), the CF Foundation (to J.M.P.), and Novartis (to J.K.K. and J.M.P.). Also supported by the confocal imaging resources of the Core Grant for Vision Research at the University of Pittsburgh (NIH P30-EY08098). |
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| Disclosure of potential conflict of interest: Y. R. Chan has received research support from the Howard Hughes Medical Institute and the National Institutes of Health (NIH) and has received payment from Novartis for contract performance of experiments. S. R. Duncan and K. Lathrop have received research support from the NIH. J. M. Pilewski has received research support from the Cystic Fibrosis Foundation and the NIH. J. K. Kolls has received research support from the NIH, is chair of the board for MiniVax, is coinventor on a patent submitted by Louisiana State University Health Sciences Center, and has received travel compensation from MiniVax. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 4
P. 1117 - avril 2013 Retour au numéro
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