Interleukin-17A modulates human airway epithelial responses to human rhinovirus infection

2007 ◽  
Vol 293 (2) ◽  
pp. L505-L515 ◽  
Author(s):  
Shahina Wiehler ◽  
David Proud
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Memory T Cells ◽  
Neutrophil Infiltration ◽  
Human Rhinovirus ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Activated T Cells ◽  
Obstructive Pulmonary Disease ◽  
Immature Dendritic Cells

Human rhinovirus (HRV) infections are associated with exacerbations of asthma and chronic obstructive pulmonary disease that are characterized by a selective neutrophil infiltration. IL-17A, a cytokine derived primarily from activated T cells, has been linked to neutrophilic inflammation of the airways. We hypothesized that IL-17A alters the response of HRV-infected epithelial cells to modulate airway inflammatory cell populations. IL-17A synergistically enhanced HRV-16-induced epithelial production of the neutrophil chemoattractant, IL-8, as well as human β-defensin-2 (HBD-2), a chemoattractant for immature dendritic cells and memory T cells, but suppressed viral production of the eosinophil chemoattractant, RANTES. These effects were not due to alterations of viral uptake or replication by IL-17A. The synergy between HRV-16 and IL-17A for IL-8 protein production was both dose- and time-dependent. IL-8 induction by IL-17A or HRV-16, alone and in combination, was reduced by inhibitors of the p38 and p44/42 MAPK pathways. By contrast, induction of HBD-2 depended on the activation of the p38 and JNK pathways. The ability of IL-17A to synergistically enhance HRV-induced IL-8 is mediated posttranscriptionally, since IL-8 promoter activation by the combination of the two stimuli was merely additive, whereas the combination of IL-17A and HRV-16 led to stabilization of IL-8 mRNA. Similarly, stimulation of HBD-2 promoter constructs by the combination of IL-17A and HRV-16 was no more than the sum of the individual responses. Further studies are needed to examine HBD-2 mRNA stability. Taken together, these data represent the first demonstration that IL-17A can modify epithelial responses to HRV in a manner that would be expected to favor the recruitment of neutrophils, immature dendritic cells, and memory T cells to the airways.

β-Defensins: Linking Innate and Adaptive Immunity Through Dendritic and T Cell CCR6

Science ◽  
1999 ◽  
Vol 286 (5439) ◽  
pp. 525-528 ◽  
Author(s):  
D. Yang ◽  
O. Chertov ◽  
S. N. Bykovskaia ◽  
Q. Chen ◽  
M. J. Buffo ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cytoplasmic Membrane ◽  
Memory T Cells ◽  
Innate And Adaptive Immunity ◽  
Adaptive Immune ◽  
Microbial Invasion ◽  
Immature Dendritic Cells ◽  
Chemokine Ligand

Defensins contribute to host defense by disrupting the cytoplasmic membrane of microorganisms. This report shows that human β-defensins are also chemotactic for immature dendritic cells and memory T cells. Human β-defensin was selectively chemotactic for cells stably transfected to express human CCR6, a chemokine receptor preferentially expressed by immature dendritic cells and memory T cells. The β-defensin–induced chemotaxis was sensitive to pertussis toxin and inhibited by antibodies to CCR6. The binding of iodinated LARC, the chemokine ligand for CCR6, to CCR6-transfected cells was competitively displaced by β-defensin. Thus, β-defensins may promote adaptive immune responses by recruiting dendritic and T cells to the site of microbial invasion through interaction with CCR6.

Increased production of TGF-β and apoptosis of T lymphocytes isolated from peripheral blood in COPD

2003 ◽  
Vol 285 (2) ◽  
pp. L492-L499 ◽  
Author(s):  
S. J. Hodge ◽  
G. L. Hodge ◽  
P. N. Reynolds ◽  
R. Scicchitano ◽  
M. Holmes
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Fas Ligand ◽  
Transforming Growth Factor ◽  
Annexin V ◽  
Peripheral Circulation ◽  
Chronic Obstructive ◽  
Activated T Cells ◽  
Obstructive Pulmonary Disease ◽  
Tnf Α

Chronic obstructive pulmonary disease (COPD) is associated with inflammation of airway epithelium, including an increase in the number of intraepithelial T cells. Increased apoptosis of these T cells has been reported in the airways in COPD, and although this process is critical for clearing excess activated T cells, excessive rates of apoptosis may result in unbalanced cellular homeostasis, defective clearance of apoptotic material by monocytes/macrophages, secondary necrosis, and prolongation of the inflammatory response. Lymphocytes are known to traffic between the airway and the peripheral circulation, thus we hypothesized that in COPD, circulating T cells may show an increased propensity to undergo apoptosis. We analyzed phytohemagglutinin (PHA)-stimulated peripheral blood T cells from COPD patients and controls for apoptosis using flow cytometry and staining with annexin V and 7-aminoactinomycin D. As several pathways are involved in induction of apoptosis of T cells, including transforming growth factor (TGF)-β/TGF receptor (TGFR), TNF-α/TNFR1, and Fas/Fas ligand, these mediators were also investigated in peripheral blood samples from these subject groups. Significantly increased apoptosis of PHA-stimulated T cells was observed in COPD (annexin positive 75.0 ± 14.7% SD vs. control 50.2 ± 21.8% SD, P = 0.006), along with upregulation of TNF-α/TNFR1, Fas, and TGFR. Monocyte production of TGF-β was also increased. In conclusion we have demonstrated the novel finding of increased apoptosis of stimulated T cells in COPD and have also shown that the increased T-cell death may be associated with upregulation of apoptotic pathways, TGF-β, TNF-α, and Fas in the peripheral blood in COPD.

HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages

10.1038/nm822 ◽  
2003 ◽  
Vol 9 (2) ◽  
pp. 191-197 ◽  
Author(s):  
Elena Izmailova ◽  
Frederic M.N. Bertley ◽  
Qian Huang ◽  
Norbert Makori ◽  
Christopher J. Miller ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Activated T Cells ◽  
Immature Dendritic Cells ◽  
Hiv 1

Mast cells and T-cell expansion

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2497-2498
Author(s):  
Susumu Nakae ◽  
Keisuke Oboki ◽  
Hirohisa Saito
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Mast Cells ◽  
Cell Expansion ◽  
Memory T Cells ◽  
T Cell Expansion

IgE/antigen-FcϵRI crosslinking promotes antigen internalization and apoptosis in mouse mast cells. Dendritic cells uptake the apoptotic mast cells carrying internalized antigens, and thus can efficiently present the antigens to memory T cells.

scholarly journals Overproduction of growth differentiation factor 15 promotes human rhinovirus infection and virus-induced inflammation in the lung

2018 ◽  
Vol 314 (3) ◽  
pp. L514-L527 ◽  
Author(s):  
Qun Wu ◽  
Di Jiang ◽  
Niccolette R. Schaefer ◽  
Laura Harmacek ◽  
Brian P. O’Connor ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Human Rhinovirus ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Growth Differentiation Factor 15 ◽  
Human Airway ◽  
Differentiation Factor ◽  
Human Airway Epithelial Cells

Human rhinovirus (HRV) is the most common virus contributing to acute exacerbations of chronic obstructive pulmonary disease (COPD) nearly year round, but the mechanisms have not been well elucidated. Recent clinical studies suggest that high levels of growth differentiation factor 15 (GDF15) protein in the blood are associated with an increased yearly rate of all-cause COPD exacerbations. Therefore, in the current study, we investigated whether GDF15 promotes HRV infection and virus-induced lung inflammation. We first examined the role of GDF15 in regulating host defense and HRV-induced inflammation using human GDF15 transgenic mice and cultured human GDF15 transgenic mouse tracheal epithelial cells. Next, we determined the effect of GDF15 on viral replication, antiviral responses, and inflammation in human airway epithelial cells with GDF15 knockdown and HRV infection. Finally, we explored the signaling pathways involved in airway epithelial responses to HRV infection in the context of GDF15. Human GDF15 protein overexpression in mice led to exaggerated inflammatory responses to HRV, increased infectious particle release, and decreased IFN-λ2/3 (IL-28A/B) mRNA expression in the lung. Moreover, GDF15 facilitated HRV replication and inflammation via inhibiting IFN-λ1/IL-29 protein production in human airway epithelial cells. Lastly, Smad1 cooperated with interferon regulatory factor 7 (IRF7) to regulate airway epithelial responses to HRV infection partly via GDF15 signaling. Our results reveal a novel function of GDF15 in promoting lung HRV infection and virus-induced inflammation, which may be a new mechanism for the increased susceptibility and severity of respiratory viral (i.e., HRV) infection in cigarette smoke-exposed airways with GDF15 overproduction.

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