Lung adenocarcinoma‐related TNF‐α‐dependent inflammation upregulates MHC‐II on alveolar type II cells through CXCR‐2 to contribute to Treg expansion
| Autor: | Can Wang, Xiuqing Wang, Mei Zhao, Ping Lv, Ningfei Guo, Lingxiao Xing, Haitao Shen, Bowei Liu, Xianghong Zhang, Xiaojing Han, Xiaoyi Liu, Yue Wen, Athena M. Soulika, Lifei Kang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lung Neoplasms Adenocarcinoma of Lung chemical and pharmacologic phenomena Inflammation medicine.disease_cause T-Lymphocytes Regulatory Biochemistry Receptors Interleukin-8B Immune tolerance Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Genetics medicine Animals Humans Molecular Biology Mice Inbred BALB C Lung Tumor Necrosis Factor-alpha Chemistry Histocompatibility Antigens Class II FOXP3 HLA-DR Antigens In vitro Up-Regulation Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Alveolar Epithelial Cells Cancer research Female Tumor necrosis factor alpha medicine.symptom Carcinogenesis 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | The FASEB Journal. 34:12197-12213 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.202000166rr |
| Popis: | MHC-II on alveolar type-II (AT-II) cells is associated with immune tolerance in an inflammatory microenvironment. Recently, we found TNF-α upregulated MHC-II in AT-II in vitro. In this study, we explored whether TNF-α-mediated inflammation upregulates MHC-II on AT-II cells to trigger Treg expansion in inflammation-driven lung adenocarcinoma (IDLA). Using urethane-induced mice IDLA model, we found that IDLA cells mainly arise from AT-II cells, which are the major source of MHC-II. Blocking urethane-induced inflammation by TNF-α neutralization inhibited tumorigenesis and reversed MHC-II upregulation on tumor cells of AT-II cellular origin in IDLA. MHC-II-dependent AT-II cells were isolated from IDLA-induced Treg expansion. In human LA samples, we found high expression of MHC-II in tumor cells of AT-II cellular origin, which was correlated with increased Foxp3+ T cells infiltration as well as CXCR-2 expression. CXCR-2 and MHC-II colocalization was observed in inflamed lung tissue and IDLA cells of AT-II cellular origin. Furthermore, at the pro-IDLA inflammatory stage, TNF-α-neutralization or CXCR-2 deficiency inhibited the upregulation of MHC-II on AT-II cells in inflamed lung tissue. Thus, tumor cells of AT-II cellular origin contribute to Treg expansion in an MHC-II-dependent manner in TNF-α-mediated IDLA. At the pro-tumor inflammatory stage, TNF-α-dependent lung inflammation plays an important role in MHC-II upregulation on AT-II cells. |
| Databáze: | OpenAIRE |
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