Blocking CD40 Alleviates Th1 and Th17 Cell Responses in Elastin Peptide-Induced Murine Emphysema

Abstract

Tingting Ma,1,2,* Hui Zhang,3,* Yuqing Weng,2,* Shudan Tang,3 Jinshan Mao,2 Xin Feng,3 Yuxin Zhang,4 Jianquan Zhang1 1Department of Respiratory and Critical Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518000, People’s Republic of China; 2Department of Respiratory and Critical Medicine, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, People’s Republic of China; 3Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 4The First Clinical Medical College, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianquan Zhang, Department of Respiratory and Critical Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518000, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: To investigate the role of the CD40-CD40 ligand (CD40L) pathway in the regulation of Th1, Th17, and regulatory T (Treg)-cell responses in an elastin peptide (EP)-induced autoimmune emphysema mouse model.Methods: BALB/c mice were transnasally treated with EP on day 0, injected intravenously with anti-CD40 antibody via the tail vein on day 33, and sacrificed on day 40. The severity of emphysema was evaluated by determining the mean linear intercept (MLI) and destructive index (DI) from lung sections. The proportions of myeloid dendritic cells (mDCs) and Th1, Th17, and Treg cells in the blood, spleen, and lungs were determined via flow cytometry. The levels of the cytokines interleukin (IL)-6, IL-17, interferon (IFN)-γ, and transforming growth factor (TGF)-β were detected via enzyme-linked immunosorbent assay. Ifnγ, IL17a, Rorγt and Foxp3 transcription levels were detected via polymerase chain reaction.Results: CD40+ mDCs accumulated in the lungs of EP-stimulated mice. Blocking the CD40-CD40L pathway with an anti-CD40 antibody alleviated Th1 and Th17 responses; increased the proportion of Treg cells; decreased MLI and DI; reduced the levels of cytokines IL-6, IL-17, and IFN-γ as well as the transcription levels of Ifnγ, IL17a, and Rorγt; and upregulated the expression of TGF-β and Foxp3.Conclusion: The CD40-CD40L pathway could play a critical role in Th1, Th17 and Treg cell dysregulation in EP-mediated emphysema and could be a potential therapeutic target.Keywords: elastin peptide, dendritic cell, Cluster of Differentiation 40, CD40, Th cell, emphysema

Keywords

• elastin peptide
• dendritic cell
• cluster of differentiation 40;cd40
• th cell
• emphysema