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Your search keyword '"Zhiyi Liu"' showing total 2 results
Start Over Author "Zhiyi Liu" Publication Year Range Last 3 years Journal journal of clinical investigation
2 results on '"Zhiyi Liu"'

1. Reprogramming alveolar macrophage responses to TGF-β reveals CCR2+ monocyte activity that promotes bronchiolitis obliterans syndrome

Author

Zhiyi Liu, Fuyi Liao, Jihong Zhu, Dequan Zhou, Gyu Seong Heo, Hannah P. Leuhmann, Davide Scozzi, Antanisha Parks, Ramsey Hachem, Derek E. Byers, Laneshia K. Tague, Hrishikesh S. Kulkarni, Marlene Cano, Brian W. Wong, Wenjun Li, Howard J. Haung, Alexander S. Krupnick, Daniel Kreisel, Yongjian Liu, and Andrew E. Gelman

Subjects
Mice, Receptors, CCR2, Transforming Growth Factor beta, Macrophages, Alveolar, Animals, General Medicine, Decorin, Bronchiolitis Obliterans, Receptors, Transforming Growth Factor beta, Granzymes, Monocytes, Lung Transplantation
Abstract

Bronchiolitis obliterans syndrome (BOS) is a major impediment to lung transplant survival and is generally resistant to medical therapy. Extracorporeal photophoresis (ECP) is an immunomodulatory therapy that shows promise in stabilizing BOS patients, but its mechanisms of action are unclear. In a mouse lung transplant model, we show that ECP blunts alloimmune responses and inhibits BOS through lowering airway TGF-β bioavailability without altering its expression. Surprisingly, ECP-treated leukocytes were primarily engulfed by alveolar macrophages (AMs), which were reprogrammed to become less responsive to TGF-β and reduce TGF-β bioavailability through secretion of the TGF-β antagonist decorin. In untreated recipients, high airway TGF-β activity stimulated AMs to express CCL2, leading to CCR2+ monocyte-driven BOS development. Moreover, we found TGF-β receptor 2-dependent differentiation of CCR2+ monocytes was required for the generation of monocyte-derived AMs, which in turn promoted BOS by expanding tissue-resident memory CD8+ T cells that inflicted airway injury through Blimp-1-mediated granzyme B expression. Thus, through studying the effects of ECP, we have identified an AM functional plasticity that controls a TGF-β-dependent network that couples CCR2+ monocyte recruitment and differentiation to alloimmunity and BOS.

Published
2022

2. B cells mediate lung ischemia/reperfusion injury by recruiting classical monocytes via synergistic B cell receptor/TLR4 signaling.

Author

Farahnak, Khashayar, Yun Zhu Bai, Yuhei Yokoyama, Morkan, Deniz B., Zhiyi Liu, Amrute, Junedh M., De Filippis Falcon, Alejandro, Yuriko Terada, Fuyi Liao, Wenjun Li, Shepherd, Hailey M., Hachem, Ramsey R., Puri, Varun, Lavine, Kory J., Gelman, Andrew E., Bharat, Ankit, Kreisel, Daniel, and Nava, Ruben G.

Subjects
*B cells, *REPERFUSION injury, *CELL communication, *MONOCYTES, *LUNGS, *LUNG transplantation
Abstract

Ischemia/reperfusion injury-mediated (IRI-mediated) primary graft dysfunction (PGD) adversely affects both short- and long-term outcomes after lung transplantation, a procedure that remains the only treatment option for patients suffering from end-stage respiratory failure. While B cells are known to regulate adaptive immune responses, their role in lung IRI is not well understood. Here, we demonstrated by intravital imaging that B cells are rapidly recruited to injured lungs, where they extravasate into the parenchyma. Using hilar clamping and transplant models, we observed that lung-infiltrating B cells produce the monocyte chemokine CCL7 in a TLR4-TRIF-dependent fashion, a critical step contributing to classical monocyte (CM) recruitment and subsequent neutrophil extravasation, resulting in worse lung function. We found that synergistic BCR-TLR4 activation on B cells is required for the recruitment of CMs to the injured lung. Finally, we corroborated our findings in reperfused human lungs, in which we observed a correlation between B cell infiltration and CM recruitment after transplantation. This study describes a role for B cells as critical orchestrators of lung IRI. As B cells can be depleted with currently available agents, our study provides a rationale for clinical trials investigating B cell-targeting therapies. [ABSTRACT FROM AUTHOR]

Published
2024
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