Review
Immunology
Yingzi Chen, Fan Li, Mengqing Hua, Meng Liang, Chuanwang Song
Summary: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor that induces the differentiation of bone marrow progenitor cells into granulocytes and macrophages. However, it is now known that GM-CSF has multiple origins and pleiotropic effects. GM-CSF activates JAK2 and induces nuclear signals through JAK-STAT, MAPK, PI3K, and other pathways. GM-CSF plays a crucial role in interstitial lung disease, allergic lung disease, alcoholic lung disease, and pulmonary infections caused by bacteria, fungi, and viruses. This article reviews the latest understanding of the relationship between GM-CSF and lung homeostasis and diseases, highlighting the broader functions of GM-CSF beyond its name suggests.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Xinmei Huang, Mengshu Cao, Yonglong Xiao
Summary: Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disorder characterized by surfactant accumulation in the alveoli. Alveolar macrophages (AMs) play a crucial role in PAP pathogenesis, particularly in cholesterol clearance and surfactant homeostasis. Novel therapies targeting GM-CSF signaling, cholesterol metabolism, and immune modulation of AMs are being developed to address this disease.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Physiology
Kenjiro Shima, Paritha Arumugam, Anthony Sallese, Yuko Horio, Yan Ma, Cole Trapnell, Matthew Wessendarp, Claudia Chalk, Cormac McCarthy, Brenna C. Carey, Bruce C. Trapnell, Takuji Suzuki
Summary: Hereditary pulmonary alveolar proteinosis (hPAP) is a rare disorder caused by mutations in GM-CSF receptor subunit alpha/beta genes, resulting in impaired surfactant clearance and respiratory failure. Through mouse models, it was found that homozygous Csf2ra gene disruption caused lung disease similar to hPAP in children with CSF2RA mutations, while heterozygous gene had no effect. Pulmonary macrophage transplantation restored GM-CSF responsiveness and showed potential as a therapy for hPAP.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Critical Care Medicine
Cormac McCarthy, Brenna C. Carey, Bruce C. Trapnell
Summary: Autoimmune pulmonary alveolar proteinosis is a rare disease characterized by dysfunction of myeloid cells, abnormal accumulation of pulmonary surfactant, and innate immune deficiency. Research has brought this disease from obscurity to a paradigm of molecular pathogenesis-based diagnosis and treatment. The low prevalence and nonspecific symptoms make diagnosis challenging and delay accurate treatment.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Multidisciplinary Sciences
Saori Sakaue, Etsuro Yamaguchi, Yoshikazu Inoue, Meiko Takahashi, Jun Hirata, Ken Suzuki, Satoru Ito, Toru Arai, Masaki Hirose, Yoshinori Tanino, Takefumi Nikaido, Toshio Ichiwata, Shinya Ohkouchi, Taizou Hirano, Toshinori Takada, Satoru Miyawaki, Shogo Dofuku, Yuichi Maeda, Takuro Nii, Toshihiro Kishikawa, Kotaro Ogawa, Tatsuo Masuda, Kenichi Yamamoto, Kyuto Sonehara, Ryushi Tazawa, Konosuke Morimoto, Masahiro Takaki, Satoshi Konno, Masaru Suzuki, Keisuke Tomii, Atsushi Nakagawa, Tomohiro Handa, Kiminobu Tanizawa, Haruyuki Ishii, Manabu Ishida, Toshiyuki Kato, Naoya Takeda, Koshi Yokomura, Takashi Matsui, Masaki Watanabe, Hiromasa Inoue, Kazuyoshi Imaizumi, Yasuhiro Goto, Hiroshi Kida, Tomoyuki Fujisawa, Takafumi Suda, Takashi Yamada, Yasuomi Satake, Hidenori Ibata, Nobuyuki Hizawa, Hideki Mochizuki, Atsushi Kumanogoh, Fumihiko Matsuda, Koh Nakata, Tomomitsu Hirota, Mayumi Tamari, Yukinori Okada
Summary: Autoimmune pulmonary alveolar proteinosis (aPAP) is a complex lung disease caused by abnormal surfactant homeostasis. In a genome-wide association study in a Japanese cohort, variants in the MHC were found and suggested a predisposition to abnormal antibody production.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, General & Internal
Shixu Liu, Xiangning Cui, Kun Xia, Dandan Wang, Jing Han, Xiaoyan Yao, Xiaohong Liu, Lingjie Bian, Jinzhi Zhang, Guangxi Li
Summary: The study reveals that research on PAP is flourishing, and international cooperation is expected to deepen and strengthen in the future. Future research hotspots include the etiology and pathogenesis of PAP, current and emerging therapies, especially novel pathogenesis-based options.
FRONTIERS IN MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Cameron Livingstone, Carmela Corallo, Miranda Siemienowicz, David Pilcher, Robert G. Stirling
Summary: This report provides the largest published experience of sargramostim use in Australia for pulmonary alveolar proteinosis, highlighting both the potential advantages and barriers of this pharmacological treatment option. Subjective improvement in symptoms and radiographical improvement were reported in the majority of patients, although significant improvement in pulmonary function testing was not observed. Careful patient selection and treatment outcome assessment are needed due to drug scarcity and high drug cost as potential barriers to accessing this treatment. Routine assessment of validated patient symptom scores along with objective physiological measures is recommended to predict response to treatment and guide management.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Respiratory System
Axelle Mabo, Raphael Borie, Lidwine Wemeau-Stervinou, Yurdaguel Uzunhan, Emmanuel Gomez, Gregoire Prevot, Martine Reynaud-Gaubert, Julie Traclet, Emmanuel Bergot, Jacques Cadranel, Sylvain Marchand-Adam, Anne Bergeron, Elodie Blanchard, Benjamin Bondue, Philippe Bonniaud, Arnaud Bourdin, Pierre Regis Burgel, Sandrine Hirschi, Charles Hugo Marquette, Sebastien Quetant, Hilario Nunes, Cecile Chenivesse, Bruno Crestani, Yoann Guirriec, Delphine Monnier, Cedric Menard, Pierre Tattevin, Vincent Cottin, David Luque Paz, Stephane Jouneau
Summary: This study investigated the characteristics and clinical outcomes of patients diagnosed with autoimmune pulmonary alveolar proteinosis (aPAP) and identified risk factors associated with opportunistic infections. The results showed that a large proportion of patients developed infections, including opportunistic infections, with Nocardia spp being the main pathogen. Male gender was found to be associated with opportunistic infections. The study highlights the importance of systematically searching for slow-growing bacteria in bronchoalveolar lavage or whole lung lavage.
Article
Respiratory System
Helene Salvator, Aristine Cheng, Lindsey B. Rosen, Peter R. Williamson, John E. Bennett, Anuj Kashyap, Li Ding, Kyung J. Kwon-Chung, Ho Namkoong, Christa S. Zerbe, Steven M. Holland
Summary: This study found that anti-GM-CSF antibodies in acquired pulmonary alveolar proteinosis (PAP), cryptococcosis, and nocardiosis were similar, despite different clinical manifestations. The neutralizing effect of anti-GM-CSF antibodies remained relatively constant over time, regardless of targeted treatments and variations in antibody levels.
RESPIRATORY RESEARCH
(2022)
Article
Medicine, Research & Experimental
Tarani Kanta Barman, Amit K. Singh, Jesse L. Bonin, Tanvir Noor Nafiz, Sharon L. Salmon, Dennis W. Metzger
Summary: This study found that coinfection of SARS-CoV-2 and Streptococcus pneumoniae leads to lung inflammation and death, and the treatment methods differ. Treatment with murine GM-CSF can reduce bacteria and pathology, partially protecting from death, but therapeutic targeting of IFNs does not work. Combined vaccination provides 100% protection against subsequent coinfection.
Review
Immunology
Ali Ataya, Vijaya Knight, Brenna C. Carey, Elinor Lee, Elizabeth J. Tarling, Tisha Wang
Summary: The article reviews the role of GM-CSF in aPAP pathogenesis and pulmonary homeostasis, as well as the increased incidence of infections.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Michal Scur, Ahmad Bakur Mahmoud, Sayanti Dey, Farah Abdalbarri, Iona Stylianides, Daniel Medina-Luna, Gayani S. Gamage, Aaron Woblistin, Alexa N. M. Wilson, Haggag S. Zein, Ashley Stueck, Andrew Wight, Oscar A. Aguilar, Francesca Di Cara, Brendon D. Parsons, Mir Munir A. Rahim, James R. Carlyle, Andrew P. Makrigiannis
Summary: This study reveals that the absence of NKR-P1B leads to impaired response of alveolar macrophages (AM) to pneumococcal infection, resulting in more severe infection. NKR-P1B plays a crucial role in regulating the metabolism of AM and the signaling axis between AM and alveolar type-II pneumocytes is essential for maintaining the normal function of AM.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Nutthakarn Suwankitwat, Stephen Libby, H. Denny Liggitt, Alan Avalos, Alanna Ruddell, Jason W. Rosch, Heon Park, Brian M. Iritani
Summary: Deficiency of Hem-1 leads to pulmonary alveolar proteinosis due to impaired development of alveolar macrophages, resulting in reduced migration of related cells and increased morbidity following pathogen challenges.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Allergy
Yeon Duk Woo, Jaemoon Koh, Jae Sung Ko, Sehui Kim, Kyeong Cheon Jung, Yoon Kyung Jeon, Hye Young Kim, Ho Lee, Chang Woo Lee, Doo Hyun Chung
Summary: The study revealed that Ssu72 fine-tunes GMCSFR signaling by regulating the development, maturation, and mitochondrial functions of alveolar macrophages, thereby controlling allergic airway inflammation.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Pediatrics
Fook-Choe Cheah, Pietro Presicce, Tian-Lee Tan, Brenna C. Carey, Suhas G. Kallapur
Summary: The study found that exposure to GM-CSF antenatally results in accumulation of immature macrophages in the fetal lung interstitium. Lack of GM-CSF did not eliminate but delayed the transitioning of interstitial macrophages. These results suggest that other perinatal factors may play a role in modulating the maturation of alveolar macrophages in the developing fetal lung.
FRONTIERS IN PEDIATRICS
(2021)
Editorial Material
Allergy
David P. Huston, Vito Sabato
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2018)
Editorial Material
Allergy
Ashwini Komarla, Julie Y. Patel, David P. Huston
CURRENT ALLERGY AND ASTHMA REPORTS
(2009)
Editorial Material
Allergy
Julie Y. Patel, Sapandeep K. Singh, David P. Huston
CURRENT ALLERGY AND ASTHMA REPORTS
(2010)
Editorial Material
Allergy
David P. Huston
CURRENT ALLERGY AND ASTHMA REPORTS
(2011)
Review
Allergy
Zhaleh J. Amini-Vaughan, Margarita Martinez-Moczygemba, David P. Huston
CURRENT ALLERGY AND ASTHMA REPORTS
(2012)
Review
Allergy
Jessica L. Cromheecke, Kathleen T. Nguyen, David P. Huston
CURRENT ALLERGY AND ASTHMA REPORTS
(2014)
Article
Immunology
Margarita Martinez-Moczygemba, Minh L. Doan, Okan Elidemir, Leland L. Fan, Sau Wai Cheung, Jonathan T. Lei, James P. Moore, Ghamartaj Tavana, Lora R. Lewis, Yiming Zhu, Donna M. Muzny, Richard A. Gibbs, David P. Huston
JOURNAL OF EXPERIMENTAL MEDICINE
(2008)
Article
Immunology
Yui-Hsi Wang, Kui Shin Voo, Bo Liu, Chun-Yu Chen, Burcin Uygungil, William Spoede, Jonathan A. Bernstein, David P. Huston, Yong-Jun Liu
JOURNAL OF EXPERIMENTAL MEDICINE
(2010)
Editorial Material
Medicine, General & Internal
David P. Huston, Linda S. Cox
JAMA INTERNAL MEDICINE
(2014)
Editorial Material
Allergy
David P. Huston
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2019)
Article
Education, Scientific Disciplines
Steve A. Maxwell, Robin Fuchs-Young, Gregg B. Wells, Geoffrey M. Kapler, Gloria M. Conover, Sheila Green, Catherine Pepper, Barbara Gastel, David P. Huston
Summary: The course Medical Student Grand Rounds (MSGR) helps medical students develop critical thinking skills and integrate basic research by training them to find, evaluate, and present relevant medical literature.
Article
Engineering, Biomedical
Dixita Ishani Viswanath, Hsuan-Chen Liu, David P. Huston, Corrine Ying Xuan Chua, Alessandro Grattoni
Summary: Landmark successes in oncoimmunology have led to the development of cancer vaccines using biomaterials to enhance the host immune system against tumors. This review focuses on strategies to attract dendritic cells, activate them against tumor-specific antigens, and stimulate T cells in secondary lymphoid organs. Personalized cancer vaccines have the potential to generate long-term systemic immunity against patient- and tumor-specific antigens.
Article
Pharmacology & Pharmacy
David L. L. Goldblatt, Gabriella Valverde Ha, Shradha Wali, Vikram V. V. Kulkarni, Michael K. K. Longmire, Ana M. M. Jaramillo, Rosha P. P. Chittuluru, Adrienne Fouts, Margarita Martinez-Moczygemba, Jonathan T. T. Lei, David P. P. Huston, Michael J. J. Tuvim, Burton F. F. Dickey, Scott E. E. Evans
Summary: Allergic asthma is a chronic inflammatory respiratory disease characterized by eosinophilic infiltration and increased mucus production. Research has shown that a combination treatment of Pam2 and ODN can reduce allergic immune responses and lower sensitivity to allergens.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Yui-Hsi Wang, Pornpimon Angkasekwinai, Ning Lu, Kui Shin Voo, Kazuhiko Arima, Shino Hanabuchi, Andreas Hippe, Chris J. Corrigan, Chen Dong, Bernhard Homey, Zhengbin Yao, Sun Ying, David P. Huston, Yong-Jun Liu
JOURNAL OF EXPERIMENTAL MEDICINE
(2007)