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. 2014 May 13;9(5):e97707.
doi: 10.1371/journal.pone.0097707. eCollection 2014.

γδ T cells are required for pulmonary IL-17A expression after ozone exposure in mice: role of TNFα

Joel A Mathews  1 , Alison S Williams  1 , Jeffrey D Brand  1 , Allison P Wurmbrand  1 , Lucas Chen  1 , Fernanda Mc Ninin  1 , Huiqing Si  1 , David I Kasahara  1 , Stephanie A Shore  1
Affiliations

γδ T cells are required for pulmonary IL-17A expression after ozone exposure in mice: role of TNFα

Joel A Mathews et al. PLoS One. .

Abstract

Ozone is an air pollutant that causes pulmonary symptoms. In mice, ozone exposure causes pulmonary injury and increases bronchoalveolar lavage macrophages and neutrophils. We have shown that IL-17A is important in the recruitment of neutrophils after subacute ozone exposure (0.3 ppm for 24-72 h). We hypothesized that γδ T cells are the main producers of IL-17A after subacute ozone. To explore this hypothesis we exposed wildtype mice and mice deficient in γδ T cells (TCRδ-/-) to ozone or room air. Ozone-induced increases in BAL macrophages and neutrophils were attenuated in TCRδ-/- mice. Ozone increased the number of γδ T cells in the lungs and increased pulmonary Il17a mRNA expression and the number of IL-17A+ CD45+ cells in the lungs and these effects were abolished in TCRδ-/- mice. Ozone-induced increases in factors downstream of IL-17A signaling, including G-CSF, IL-6, IP-10 and KC were also decreased in TCRδ-/- versus wildtype mice. Neutralization of IL-17A during ozone exposure in wildtype mice mimicked the effects of γδ T cell deficiency. TNFR2 deficiency and etanercept, a TNFα antagonist, also reduced ozone-induced increases in Il17a mRNA, IL-17A+ CD45+ cells and BAL G-CSF as well as BAL neutrophils. TNFR2 deficient mice also had decreased ozone-induced increases in Ccl20, a chemoattractant for IL-17A+ γδ T cells. Il17a mRNA and IL-17A+ γδ T cells were also lower in obese Cpefat versus lean WT mice exposed to subacute ozone, consistent with the reduced neutrophil recruitment observed in the obese mice. Taken together, our data indicate that pulmonary inflammation induced by subacute ozone requires γδ T cells and TNFα-dependent recruitment of IL-17A+ γδ T cells to the lung.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Effect of γδ T cell deficiency on pulmonary inflammation and injury.
(A–C) BAL neutrophils, macrophages, and protein; (D) pulmonary Il17a mRNA expression; (E–I) BAL G-CSF, IL-6, IP-10, KC, and MCP-1. Results are mean±SEM of 4–11 mice per group. *p<0.05 versus genotype-matched air-exposed mice. #p<0.05 versus WT mice with the same exposure.
Figure 2
Figure 2. Effect of O3 exposure on IL-17A positive lung cells assessed by flow cytometry.
(A) lung IL-17A+CD45+; (B) lung IL-17A+ γδ T cells; (C) total lung γδ T cells. Results are mean±SEM for 3–6 air-exposed and 4–11 O3-exposed mice. *p<0.05 versus genotype-matched air-exposed mice. #p<0.05 versus WT mice with same exposure.
Figure 3
Figure 3. Effect of anti-IL-17A on O3-induced pulmonary inflammation and injury.
WT mice were injected with anti-IL-17A or isotype 24 h prior to O3 (0.3 ppm O3 for 72 h). (A) BAL macrophages and neutrophils; (B) BAL protein; (C) BAL cytokines determined by multiplex assay. Results are mean±SEM of 5–7 mice per group. #p<0.05 versus isotype control.
Figure 4
Figure 4. Impact of TNFR2 deficiency (A–C) or etanercept (D–F) on O3-induced inflammation in obese (Cpefat) and lean (WT) mice.
(A, D) BAL neutrophils; (B, E) Il17a mRNA expression; (C, F) BAL G-CSF. Results are mean±SE of data from 3–11 mice in each group.*p<0.05 versus air-exposed mice of same genotype and treatment; #p<0.05 versus exposure matched lean mice with same TNFR2 genotype or treatment; & p<0.05 versus TNFR2 sufficient (A–C) or vehicle treated mice (D–F) with same exposure and Cpe genotype.
Figure 5
Figure 5. Role of TNFα for IL-17A expression in γδ T cells.
Total number of (A) lung IL-17A+CD45+ cells; (B) lung IL-17A+ γδ T cells; and (C) total lung γδ T cells. Results are mean±SE of data from 5–6 mice in each group. #p<0.05 compared to lean mice with same TNFR2 genotype; & p<0.05 compared to TNFR2+/+ Cpe genotype matched mice.
Figure 6
Figure 6. TNFα signaling is required for expression of Il12Rβ1 and Ccl20.
(A) BAL IL-6; (B–D)) Il23 (p19) mRNA; (E–G) Ccl20 mRNA; (H) Il12Rβ1 mRNA; (I) MFI and (J) % of γδ T cells positive for IL-12Rβ1 after stimulation with TNFα Results are mean±SE of data from 3–11 mice in each group. *p<0.05 versus air exposed mice of the same genotype; #p<0.05 versus exposure matched lean mice with the same TNFR2 genotype or treatment; & p<0.05 versus WT; %<0.05 obese versus lean regardless of TNFR2 genotype.
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References

    1. Wands JM, Roark CL, Aydintug MK, Jin N, Hahn Y-S, et al. (2005) Distribution and leukocyte contacts of γδ T cells in the lung. Journal of Leukocyte Biology 78: 1086–1096. - PubMed
    1. Laan M, Cui Z-H, Hoshino H, Lötvall J, Sjöstrand M, et al. (1999) Neutrophil Recruitment by Human IL-17 Via C-X-C Chemokine Release in the Airways. The Journal of Immunology 162: 2347–2352. - PubMed
    1. Skeen MJ, Ziegler HK (1993) Induction of murine peritoneal gamma/delta T cells and their role in resistance to bacterial infection. The Journal of Experimental Medicine 178: 971–984. - PMC - PubMed
    1. Cheng P, Liu T, Zhou W-Y, Zhuang Y, Peng L-s, et al. (2012) Role of gamma-delta T cells in host response against Staphylococcus aureus-induced pneumonia. BMC Immunology 13: 38. - PMC - PubMed
    1. Koohsari H, Tamaoka M, Campbell H, Martin J (2007) The role of gammadelta T cells in airway epithelial injury and bronchial responsiveness after chlorine gas exposure in mice. Respiratory Research 8: 21. - PMC - PubMed

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