Unconventional Activation of IRE1 Enhances TH17 Responses and Promotes Airway Neutrophilia
This study found that the UPR sensor IRE1 is induced in the murine lung with fungal asthma and is highly expressed in TH17 cells relative to naïve CD4+ T cells. Cytokine (e.g. IL-23) signals induce the IRE1-XBP1s axis in a JAK2-dependent manner. This noncanonical activation of the IRE1-XBP1s pathway promotes UPRs and cytokine secretion by both human and mouse TH17 cells. Ern1 (encoding IRE1)-deficiency decreases the expression of ER stress factors and impairs the differentiation and cytokine secretion of TH17 cells. Genetic ablation of Ern1 leads to alleviated TH17 responses and airway neutrophilia in a fungal airway infl...
Source: Am J Respir Cell Mol... - April 9, 2024 Category: Respiratory Medicine Authors: Dandan Wu Xing Zhang Kourtney M Zimmerly Ruoning Wang Amanda Livingston Takao Iwawaki Ashok Kumar Xiang Wu Matthew Campen Michael A Mandell Meilian Liu Xuexian O Yang Source Type: research

Local, Quantitative Morphometry of Fibroproliferative Lung Injury Using Laminin
Am J Respir Cell Mol Biol. 2024 Apr 9. doi: 10.1165/rcmb.2023-0294MA. Online ahead of print.ABSTRACTInvestigations into the mechanisms of injury and repair in fibroproliferative disease require consideration of the spatial heterogeneity inherent in the disease. Most scoring of fibrotic remodeling in preclinical animal models rely on the modified Ashcroft score, which is a semi-quantitative scoring rubric of macroscopic resolution. The obvious limitations inherent in manual pathohistological grading have generated an unmet need for unbiased, repeatable scoring of fibroproliferative burden in tissue. Using computer vision ap...
Source: Am J Respir Cell Mol... - April 9, 2024 Category: Respiratory Medicine Authors: Brendan P Cox Riley T Hannan Noora Batrash Pearl Raichura Anne I Sperling Yun Michael Shim Jeffrey M Sturek Source Type: research

Unconventional Activation of IRE1 Enhances TH17 Responses and Promotes Airway Neutrophilia
This study found that the UPR sensor IRE1 is induced in the murine lung with fungal asthma and is highly expressed in TH17 cells relative to naïve CD4+ T cells. Cytokine (e.g. IL-23) signals induce the IRE1-XBP1s axis in a JAK2-dependent manner. This noncanonical activation of the IRE1-XBP1s pathway promotes UPRs and cytokine secretion by both human and mouse TH17 cells. Ern1 (encoding IRE1)-deficiency decreases the expression of ER stress factors and impairs the differentiation and cytokine secretion of TH17 cells. Genetic ablation of Ern1 leads to alleviated TH17 responses and airway neutrophilia in a fungal airway infl...
Source: Am J Respir Cell Mol... - April 9, 2024 Category: Respiratory Medicine Authors: Dandan Wu Xing Zhang Kourtney M Zimmerly Ruoning Wang Amanda Livingston Takao Iwawaki Ashok Kumar Xiang Wu Matthew Campen Michael A Mandell Meilian Liu Xuexian O Yang Source Type: research

DACH1 Attenuates Airway Inflammation in COPD by Activating NRF2 Signaling
This study aims to elucidate the role and underlying mechanism of DACH1 in airway inflammation of COPD. DACH1 expression was measured in lung tissues of patients with COPD. Airway epithelium-specific DACH1 knockdown mice and AAV-transfected DACH1 overexpressed mice were used to investigate its role and potential for therapeutic targeting in experimental COPD caused by CS. Furthermore, we discovered a potential mechanism of DACH1 in inflammation induced by cigarette smoke extract simulation (CSE) in vitro. Compared to non-smokers and smokers without COPD, COPD patients had reduced DACH1 expression, especially in the airway ...
Source: Am J Respir Cell Mol... - April 8, 2024 Category: Respiratory Medicine Authors: Qian Huang Yiya Gu Jixing Wu Yuan Zhan Zhesong Deng Shanshan Chen Maocuo Peng Ruonan Yang Jinkun Chen Jungang Xie Source Type: research

DACH1 Attenuates Airway Inflammation in COPD by Activating NRF2 Signaling
This study aims to elucidate the role and underlying mechanism of DACH1 in airway inflammation of COPD. DACH1 expression was measured in lung tissues of patients with COPD. Airway epithelium-specific DACH1 knockdown mice and AAV-transfected DACH1 overexpressed mice were used to investigate its role and potential for therapeutic targeting in experimental COPD caused by CS. Furthermore, we discovered a potential mechanism of DACH1 in inflammation induced by cigarette smoke extract simulation (CSE) in vitro. Compared to non-smokers and smokers without COPD, COPD patients had reduced DACH1 expression, especially in the airway ...
Source: Am J Respir Cell Mol... - April 8, 2024 Category: Respiratory Medicine Authors: Qian Huang Yiya Gu Jixing Wu Yuan Zhan Zhesong Deng Shanshan Chen Maocuo Peng Ruonan Yang Jinkun Chen Jungang Xie Source Type: research

Cell Crosstalk in Alveolar Microenvironment: From Lung Injury to Fibrosis
Am J Respir Cell Mol Biol. 2024 Apr 5. doi: 10.1165/rcmb.2023-0426TR. Online ahead of print.ABSTRACTAlveoli are complex microenvironments composed of various cell types, including epithelial, fibroblast, endothelial, and immune cells, which work together to maintain a delicate balance in the lung environment, ensuring proper growth, development, and an effective response to lung injuries. However, prolonged inflammation or aging can disrupt normal interactions between these cells, leading to impaired repair processes and a substantial decline in lung function. Therefore, it is essential to understand the key mechanisms und...
Source: Am J Respir Cell Mol... - April 5, 2024 Category: Respiratory Medicine Authors: Licheng Song Kuan Li Huaiyong Chen Lixin Xie Source Type: research

Cell Crosstalk in Alveolar Microenvironment: From Lung Injury to Fibrosis
Am J Respir Cell Mol Biol. 2024 Apr 5. doi: 10.1165/rcmb.2023-0426TR. Online ahead of print.ABSTRACTAlveoli are complex microenvironments composed of various cell types, including epithelial, fibroblast, endothelial, and immune cells, which work together to maintain a delicate balance in the lung environment, ensuring proper growth, development, and an effective response to lung injuries. However, prolonged inflammation or aging can disrupt normal interactions between these cells, leading to impaired repair processes and a substantial decline in lung function. Therefore, it is essential to understand the key mechanisms und...
Source: Am J Respir Cell Mol... - April 5, 2024 Category: Respiratory Medicine Authors: Licheng Song Kuan Li Huaiyong Chen Lixin Xie Source Type: research

Cell Crosstalk in Alveolar Microenvironment: From Lung Injury to Fibrosis
Am J Respir Cell Mol Biol. 2024 Apr 5. doi: 10.1165/rcmb.2023-0426TR. Online ahead of print.ABSTRACTAlveoli are complex microenvironments composed of various cell types, including epithelial, fibroblast, endothelial, and immune cells, which work together to maintain a delicate balance in the lung environment, ensuring proper growth, development, and an effective response to lung injuries. However, prolonged inflammation or aging can disrupt normal interactions between these cells, leading to impaired repair processes and a substantial decline in lung function. Therefore, it is essential to understand the key mechanisms und...
Source: Am J Respir Cell Mol... - April 5, 2024 Category: Respiratory Medicine Authors: Licheng Song Kuan Li Huaiyong Chen Lixin Xie Source Type: research

Disrupting the TGF β/Wnt Balance to Control the Polarity of the Cystic Fibrosis Airway Epithelium
Am J Respir Cell Mol Biol. 2024 Apr 4. doi: 10.1165/rcmb.2024-0112ED. Online ahead of print.NO ABSTRACTPMID:38574230 | DOI:10.1165/rcmb.2024-0112ED (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - April 4, 2024 Category: Respiratory Medicine Authors: Carlos M Farinha Source Type: research

Activated Clec4n < sup > hi < /sup > Neutrophils Aggravate Lung Injury in an Endothelial IGFBP7 Dependent Manner
Am J Respir Cell Mol Biol. 2024 Apr 4. doi: 10.1165/rcmb.2024-0017OC. Online ahead of print.ABSTRACTThe role of endothelial cells in Acute lung injury (ALI) has been widely elaborated, but little is known about the role of different subtypes of endothelial cells in ALI. ALI models were established by lipopolysaccharide. Single-cell RNA sequencing was used to identify differential molecules in endothelial subtypes and heterogeneity of lung immune cells. Specific antibodies were used to block IGFBP7 protein, and AAVshIGP7 was used to specifically knock down IGFBP7. Here, we found that Insulin-like growth factor binding prote...
Source: Am J Respir Cell Mol... - April 4, 2024 Category: Respiratory Medicine Authors: Linchao Yu Rui He Daoxin Wang Di Qi Source Type: research

Foxq1 Promotes Alveolar Epithelial Cell Death through Tle1-mediated Inhibition of the NF κB Signaling Pathway
Am J Respir Cell Mol Biol. 2024 Apr 4. doi: 10.1165/rcmb.2023-0317OC. Online ahead of print.ABSTRACTAcute lung injury is a common respiratory disease characterized by diffuse alveolar injury and interstitial edema, as well as a hyperinflammatory response, lung cell damage and oxidative stress. Foxq1, a member of the FOX family of transcription factors, is expressed in various tissues, such as the lungs, liver, and kidneys, and contributes to various biological processes, such as stress, metabolism, cell cycle arrest, and aging-related apoptosis. However, the role of Foxq1 in acute lung injury is unknown. We constructed ex ...
Source: Am J Respir Cell Mol... - April 4, 2024 Category: Respiratory Medicine Authors: Xi Zhu Ershi Hua Qifeng Tu Mei Liu Liqin Xu Jian Feng Source Type: research

IL-10 Counteracts IFN- γ to Alleviate Acute Lung Injury in a Viral-Bacterial Superinfection Model
Am J Respir Cell Mol Biol. 2024 Apr 4. doi: 10.1165/rcmb.2023-0437OC. Online ahead of print.ABSTRACTImmune activation is essential for lung control of viral and bacterial infection, but an overwhelming inflammatory response often leads to the onset of acute respiratory distress syndrome (ARDS). Interleukin-10 (IL-10) plays a crucial role in regulating the balance between antimicrobial immunity and immunopathology. In the current study, we have investigated the role of IL-10 in acute lung injury (ALI) induced by influenza A virus (IAV) and methicillin-resistant Staphylococcus aureus (MRSA) coinfection. This unique coinfecti...
Source: Am J Respir Cell Mol... - April 4, 2024 Category: Respiratory Medicine Authors: Michael McKelvey Md Bashir Uddin Sunil Palani Shengjun Shao Keer Sun Source Type: research

Dissecting a Brake for Airway Smooth Muscle Cell Movement
Am J Respir Cell Mol Biol. 2024 Apr 3. doi: 10.1165/rcmb.2024-0120ED. Online ahead of print.NO ABSTRACTPMID:38568237 | DOI:10.1165/rcmb.2024-0120ED (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - April 3, 2024 Category: Respiratory Medicine Authors: Dale D Tang Source Type: research

Dissecting a Brake for Airway Smooth Muscle Cell Movement
Am J Respir Cell Mol Biol. 2024 Apr 3. doi: 10.1165/rcmb.2024-0120ED. Online ahead of print.NO ABSTRACTPMID:38568237 | DOI:10.1165/rcmb.2024-0120ED (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - April 3, 2024 Category: Respiratory Medicine Authors: Dale D Tang Source Type: research

Airway Proteotypes of E-Cigarette Users Overlap with Those Found in Asthmatics
Am J Respir Cell Mol Biol. 2024 Apr;70(4):326-328. doi: 10.1165/rcmb.2023-0381LE.NO ABSTRACTPMID:38557396 | DOI:10.1165/rcmb.2023-0381LE (Source: Am J Respir Cell Mol...)
Source: Am J Respir Cell Mol... - April 1, 2024 Category: Respiratory Medicine Authors: Elise Hickman Neil E Alexis Julia E Rager Ilona Jaspers Source Type: research