Background/Purpose: Interstitial pneumonia (IP) is a chronic progressive interstitial lung disease associated with high mortality and poor prognosis. However, the exact mechanism of IP remains elusive. Recently, the pathological role of gdT cells was reported in several IP mice models. The γδT cells could produce a wide variety of cytokines, chemokines and growth factors and these cells have an important role in the regulation of the initial immune responses. In human, we previously reported that γδT cells might concern the pathogenesis of IP in systemic sclerosis patients. However, there are no reports on the properties and functional characteristics of γδT cells in pulmonary fibrosis. The purpose of this study is to clarify the role of γδT cells in bleomycin-induced IP model mice.

Methods: 1.C57BL/6 (WT) mice were injected with bleomycin (1.25mg/kg, intratracheally). After 3, 7, 14 and 21 days, the phenotypes of pulmonary γδT cells were examined by flow cytometry (FCM). 2.WT and TCRδ deficient (TCRδ^-/-) mice were injected with bleomycin and the pathological findings were examined. 3.WT and TCRδ^-/- mice were injected with bleomycin. At 3, 7, 14, 21 days, pulmonary Th17 (IL-17A⁺ CD4⁺ T) and Treg (Foxp3⁺ CD4⁺) cells were analyzed by FCM. 4.Splenic CD4⁺T cells isolated from WT mice were co-cultured with γδT cells in condition of Th17 cell differentiation.

Results: 1.The number of pulmonary γδT cells increased at day3, 7, 14 after bleomycin exposure (p<0.05, p<0.05 and p<0.05, respectively). At 3 days after bleomycin exposure, pulmonary IFN-γ⁺ γδT cells increased (p<0.05). On the other hands, pulmonary IL-17A⁺ γδT cells increased at 7, 14 and 21 days after bleomycin exposure (p<0.05, p<0.05 and p<0.05, respectively). 2.TCRδ^-/- mice showed pronounced hypercellularity and intimal thickening in lung parenchyma, and overproduction of collagen in lungs compared with WT mice. 3.In TCRδ^-/- mice, pulmonary IL-17A⁺ CD4⁺ T cells increased at day 7 and 14 after bleomycin exposure compared with WT mice (p<0.05 and p<0.05, respectively). Pulmonary Foxp3⁺ CD4⁺ T cells were not significantly difference between WT and TCRδ^-/- mice. 4.After co-cultured with γδT cells, the rate of IL-17A production in CD4⁺ T cells and the number of IL-17A⁺ CD4⁺T cells were significantly decreased (p<0.05 and p<0.05, respectively).

Conclusion: Pulmonary γδT cells might play a regulatory role in the generation of bleomycin induced IP model mice via the suppression of IL-17 production.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-regulatory-role-of-gammadelta-t-cells-in-bleomycin-induced-pulmonary-fibrosis/