A dynamic variation of pulmonary ACE2 is required to modulate neutrophilic inflammation in response to pseudomonas aeruginosa lung infection in mice

Journal of Immunology

Volumn 203, Issue 11, 2019, Pages 3000-3012

  Sodhi, Chhinder P ^a   Nguyen, Jenny ^b   Yamaguchi, Yukihiro ^a   Werts, Adam D ^a   Lu, Peng ^a   Ladd, Mitchell R ^a   Fulton, William B ^a   Kovler, Mark L ^a   Wang, Sanxia ^a   Prindle, Thomas ^a   Zhang, Yong ^c   Lazartigues, Eric D ^d,e   Holtzman, Michael J ^c   Alcorn, John F ^f   Hackam, David J ^a   Jia, Hongpeng ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d LOUISIANA STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e VETERANS AFFAIRS MEDICAL CENTER   (United States)

^f UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 (6 BROMO 2 PYRIDINYL) 2 CYANO N (1 PHENYLETHYL)ACRYLAMIDE; ANGIOTENSIN CONVERTING ENZYME 2; ANTIINFECTIVE AGENT; INTERLEUKIN 17; MLN 4760; RECOMBINANT ANGIOTENSIN CONVERTING ENZYME 2; STAT3 PROTEIN; UNCLASSIFIED DRUG; 2-(1-CARBOXY-2-(3-(3,5-DICHLOROBENZYL)-3H-IMIDAZOL-4-YL)ETHYLAMINO)-4-METHYLPENTANOIC ACID; DIPEPTIDYL CARBOXYPEPTIDASE; IMIDAZOLE DERIVATIVE; LEUCINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BACTERIAL PNEUMONIA; CONTROLLED STUDY; DISEASE SEVERITY; DRUG EFFECT; DRUG RESPONSE; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME BLOOD LEVEL; FEMALE; HOST RESISTANCE; INNATE IMMUNITY; LUNG INJURY; MALE; MOUSE; NEUTROPHIL; NEUTROPHIL CHEMOTAXIS; NEUTROPHILIA; NONHUMAN; PRIORITY JOURNAL; PSEUDOMONAS AERUGINOSA; ANIMAL; C57BL MOUSE; DISEASE MODEL; GENETICS; IMMUNOLOGY; INFLAMMATION; MICROBIAL SENSITIVITY TEST; PATHOLOGY; PSEUDOMONAS INFECTION; TRANSGENIC MOUSE;

ANIMALS; DISEASE MODELS, ANIMAL; FEMALE; IMIDAZOLES; IMMUNITY, INNATE; INFLAMMATION; LEUCINE; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MICROBIAL SENSITIVITY TESTS; NEUTROPHILS; PEPTIDYL-DIPEPTIDASE A; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS INFECTIONS;

EID: 85075226040     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1900579     Document Type: Article

References (75)

1. Bijani, B., H. Mozhdehipanah, H. Jahanihashemi, and S. Azizi. 2014. The impact of pneumonia on hospital stay among patients hospitalized for acute stroke. Neurosciences (Riyadh) 19: 118-123.
2. Chow, E. J., and L. A. Mermel. 2017. Hospital-acquired respiratory viral infections: Incidence, morbidity, and mortality in pediatric and adult patients. Open Forum Infect. Dis. 4: Ofx006.
3. Chughtai, M., C. U. Gwam, N. Mohamed, A. Khlopas, J. M. Newman, R. Khan, A. Nadhim, S. Shaffiy, and M. A. Mont. 2017. The epidemiology and risk factors for postoperative pneumonia. J. Clin. Med. Res. 9: 466-475.
4. Li, H., and B. Cao. 2017. Pandemic and avian influenza a viruses in humans: Epidemiology, virology, clinical characteristics, and treatment strategy. Clin. Chest Med. 38: 59-70.
5. Dick, A., H. Liu, J. Zwanziger, E. Perencevich, E. Y. Furuya, E. Larson, M. Pogorzelska-Maziarz, and P. W. Stone. 2012. Long-term survival and healthcare utilization outcomes attributable to sepsis and pneumonia. BMC Health Serv. Res. 12: 432.
6. Cassiere, H. A., and A. M. Fein. 1996. Severe community-acquired pneumonia. Curr. Opin. Pulm. Med. 2: 186-191.
7. Cilloniz, C., I. Martin-Loeches, C. Garcia-Vidal, A. San Jose, and A. Torres. 2016. Microbial etiology of pneumonia: Epidemiology, diagnosis and resistance patterns. Int. J. Mol. Sci. 17: 2120.
8. Zilberberg, M. D., and A. F. Shorr. 2013. Prevalence of multidrug-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae among specimens from hospitalized patients with pneumonia and bloodstream infections in the United States from 2000 to 2009. J. Hosp. Med. 8: 559-563.
9. Cantone, M., G. Santos, P. Wentker, X. Lai, and J. Vera. 2017. Multiplicity of mathematical modeling strategies to search for molecular and cellular insights into bacteria lung infection. [Published erratum appears in 2017 Front. Physiol. 8: 817.] Front. Physiol. 8: 645.
10. Lawrence, D. W., and J. Kornbluth. 2018. Reduced inflammation and cytokine production in NKLAM deficient mice during Streptococcus pneumoniae infection. PLoS One 13: E0194202.
11. Robinson, K. M., K. Ramanan, M. E. Clay, K. J. McHugh, M. J. Pilewski, K. L. Nickolich, C. Corey, S. Shiva, J. Wang, R. Muzumdar, and J. F. Alcorn. 2018. The inflammasome potentiates influenza/Staphylococcus aureus superinfection in mice. JCI Insight 3: E97470.
12. Mirabito Colafella, K. M., D. M. Bovée, and A. H. J. Danser. 2019. The reninangiotensin-aldosterone system and its therapeutic targets. Exp. Eye Res. 186: 107680.
13. Mowry, F. E., and V. C. Biancardi. 2019. Neuroinflammation in hypertension: The renin-angiotensin system versus pro-resolution pathways. Pharmacol. Res. 144: 279-291.
14. Rivière, G., A. Michaud, C. Breton, G. VanCamp, C. Laborie, M. Enache, J. Lesage, S. Deloof, P. Corvol, and D. Vieau. 2005. Angiotensin-converting enzyme 2 (ACE2) and ACE activities display tissue-specific sensitivity to undernutrition-programmed hypertension in the adult rat. Hypertension 46: 1169-1174.
15. Schütz, S., J. M. Le Moullec, P. Corvol, and J. M. Gasc. 1996. Early expression of all the components of the renin-angiotensin-system in human development. Am. J. Pathol. 149: 2067-2079.
16. Hilgenfeldt, U., G. Kienapfel, W. Kellermann, R. Schott, and M. Schmidt. 1987. Renin-angiotensin system in sepsis. Clin. Exp. Hypertens. A 9: 1493-1504.
17. Kim, J., J. K. Lee, E. Y. Heo, H. S. Chung, and D. K. Kim. 2016. The association of renin-angiotensin system blockades and pneumonia requiring admission in patients with COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 11: 2159-2166.
18. Ding, C., C. van 't Veer, J. J. T. H. Roelofs, M. Shukla, K. R. McCrae, A. S. Revenko, J. Crosby, and T. van der Poll. 2018. Limited role of kininogen in the host response during gram-negative pneumonia-derived sepsis. Am. J. Physiol. Lung Cell. Mol. Physiol. 314: L397-L405.
19. Perevozchikov, P. N., and V. F. Cheganov. 1988. [Parasympathetic component of the regulation of the kallikrein-kinin system in experimental pneumonia]. Biull. Eksp. Biol. Med. 106: 417-419.
20. Jia, H. 2016. Pulmonary angiotensin-converting enzyme 2 (ACE2) and inflammatory lung disease. Shock 46: 239-248.
21. Kuba, K., Y. Imai, S. Rao, H. Gao, F. Guo, B. Guan, Y. Huan, P. Yang, Y. Zhang, W. Deng, et al. 2005. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat. Med. 11: 875-879.
22. Shi, Y., B. Zhang, X. J. Chen, D. Q. Xu, Y. X. Wang, H. Y. Dong, S. R. Ma, R. H. Sun, Y. P. Hui, and Z. C. Li. 2013. Osthole protects lipopolysaccharideinduced acute lung injury in mice by preventing down-regulation of angiotensinconverting enzyme 2. Eur. J. Pharm. Sci. 48: 819-824.
23. Lambert, D. W., N. M. Hooper, and A. J. Turner. 2008. Angiotensin-converting enzyme 2 and new insights into the renin-angiotensin system. Biochem. Pharmacol. 75: 781-786.
24. Turner, A. J., S. R. Tipnis, J. L. Guy, G. Rice, and N. M. Hooper. 2002. ACEH/ ACE2 is a novel mammalian metallocarboxypeptidase and a homologue of angiotensin-converting enzyme insensitive to ACE inhibitors. Can. J. Physiol. Pharmacol. 80: 346-353.
25. Imai, Y., K. Kuba, S. Rao, Y. Huan, F. Guo, B. Guan, P. Yang, R. Sarao, T. Wada, H. Leong-Poi, et al. 2005. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 436: 112-116.
26. Gaddam, R. R., S. Chambers, and M. Bhatia. 2014. ACE and ACE2 in inflammation: A tale of two enzymes. Inflamm. Allergy Drug Targets 13: 224-234.
27. Liu, Q., J. Du, X. Yu, J. Xu, F. Huang, X. Li, C. Zhang, X. Li, J. Chang, D. Shang, et al. 2017. miRNA-200c-3p is crucial in acute respiratory distress syndrome. Cell Discov. 3: 17021.
28. Sodhi, C. P., C. Wohlford-Lenane, Y. Yamaguchi, T. Prindle, W. B. Fulton, S. Wang, P. B. McCray, Jr., M. Chappell, D. J. Hackam, and H. Jia. 2018. Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg9 bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration. Am. J. Physiol. Lung Cell. Mol. Physiol. 314: L17-L31.
29. Zhang, Y., G. Huang, L. P. Shornick, W. T. Roswit, J. M. Shipley, S. L. Brody, and M. J. Holtzman. 2007. A transgenic FOXJ1-Cre system for gene inactivation in ciliated epithelial cells. Am. J. Respir. Cell Mol. Biol. 36: 515-519.
30. Hild, M., and A. B. Jaffe. 2016. Production of 3-D airway organoids from primary human airway basal cells and their use in high-throughput screening. Curr. Protoc. Stem Cell Biol. 37: IE.9.1-IE.9.15.
31. Tan, Q., K. M. Choi, D. Sicard, and D. J. Tschumperlin. 2017. Human airway organoid engineering as a step toward lung regeneration and disease modeling. Biomaterials 113: 118-132.
32. Cetin, S., H. R. Ford, L. R. Sysko, C. Agarwal, J. Wang, M. D. Neal, C. Baty, G. Apodaca, and D. J. Hackam. 2004. Endotoxin inhibits intestinal epithelial restitution through activation of Rho-GTPase and increased focal adhesions. J. Biol. Chem. 279: 24592-24600.
33. Egan, C. E., C. P. Sodhi, M. Good, J. Lin, H. Jia, Y. Yamaguchi, P. Lu, C. Ma, M. F. Branca, S. Weyandt, et al. 2016. Toll-like receptor 4-mediated lymphocyte influx induces neonatal necrotizing enterocolitis. J. Clin. Invest. 126: 495-508.
34. Jia, H. P., D. C. Look, P. Tan, L. Shi, M. Hickey, L. Gakhar, M. C. Chappell, C. Wohlford-Lenane, and P. B. McCray, Jr. 2009. Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia. Am. J. Physiol. Lung Cell. Mol. Physiol. 297: L84-L96.
35. Yang, P., H. Gu, Z. Zhao, W. Wang, B. Cao, C. Lai, X. Yang, L. Zhang, Y. Duan, S. Zhang, et al. 2014. Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury. Sci. Rep. 4: 7027.
36. Zou, Z., Y. Yan, Y. Shu, R. Gao, Y. Sun, X. Li, X. Ju, Z. Liang, Q. Liu, Y. Zhao, et al. 2014. Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections. Nat. Commun. 5: 3594.
37. Zhang, H., and A. Baker. 2017. Recombinant human ACE2: Acing out angiotensin II in ARDS therapy. Crit. Care 21: 305.
38. Li, S. M., X. Y. Wang, F. Liu, and X. H. Yang. 2018. [ACE2 agonist DIZE alleviates lung injury induced by limb ischemia-reperfusion in mice]. Sheng Li Xue Bao 70: 175-183.
39. Tan, W. S. D., W. Liao, S. Zhou, D. Mei, and W. F. Wong. 2018. Targeting the renin-angiotensin system as novel therapeutic strategy for pulmonary diseases. Curr. Opin. Pharmacol. 40: 9-17.
40. McCarthy, M. K., L. Zhu, M. C. Procario, and J. B. Weinberg. 2014. IL-17 contributes to neutrophil recruitment but not to control of viral replication during acute mouse adenovirus type 1 respiratory infection. Virology 456-457: 259-267.
41. Roos, A. B., S. Sethi, J. Nikota, C. T. Wrona, M. G. Dorrington, C. Sandén, C. M. Bauer, P. Shen, D. Bowdish, C. S. Stevenson, et al. 2015. IL-17A and the promotion of neutrophilia in acute exacerbation of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 192: 428-437.
42. Li, X., S. He, R. Li, X. Zhou, S. Zhang, M. Yu, Y. Ye, Y. Wang, C. Huang, and M. Wu. 2016. Pseudomonas aeruginosa infection augments inflammation through miR-301b repression of c-Myb-mediated immune activation and infiltration. Nat. Microbiol. 1: 16132.
43. Mize, M. T., X. L. Sun, and J. W. Simecka. 2018. Interleukin-17A exacerbates disease severity in BALB/c mice susceptible to lung infection with mycoplasma pulmonis. Infect. Immun. 86: E00292-18.
44. Qiao, S., H. Zhang, X. Zha, W. Niu, J. Liang, G. Pang, Y. Tang, T. Liu, H. Zhao, Y. Wang, and H. Bai. 2019. Endogenous IL-17A mediated neutrophil infiltration by promoting chemokines expression during chlamydial lung infection. Microb. Pathog. 129: 106-111.
45. Jia, H., C. P. Sodhi, Y. Yamaguchi, P. Lu, M. R. Ladd, A. Werts, W. B. Fulton, S. Wang, T. Prindle, Jr., and D. J. Hackam. 2019. Toll like receptor 4 mediated lymphocyte imbalance induces Nec-induced lung injury. Shock 52: 215-223.
46. Fogli, L. K., M. S. Sundrud, S. Goel, S. Bajwa, K. Jensen, E. Derudder, A. Sun, M. Coffre, C. Uyttenhove, J. Van Snick, et al. 2013. T cell-derived IL-17 mediates epithelial changes in the airway and drives pulmonary neutrophilia. [Published erratum appears in 2013 J. Immunol. 191: 5318.] J. Immunol. 191: 3100-3111.
47. Zhang, Y., L. Zhang, J. Wu, C. Di, and Z. Xia. 2013. Heme oxygenase-1 exerts a protective role in ovalbumin-induced neutrophilic airway inflammation by inhibiting Th17 cell-mediated immune response. J. Biol. Chem. 288: 34612-34626.
48. Yan, Z., Z. Xiaoyu, S. Zhixin, Q. Di, D. Xinyu, X. Jing, H. Jing, D. Wang, Z. Xi, Z. Chunrong, and W. Daoxin. 2016. Rapamycin attenuates acute lung injury induced by LPS through inhibition of Th17 cell proliferation in mice. Sci. Rep. 6: 20156.
49. Ding, F. M., R. M. Liao, Y. Q. Chen, G. G. Xie, P. Y. Zhang, P. Shao, and M. Zhang. 2017. Upregulation of SOCS3 in lung CD4+ T cells in a mouse model of chronic PA lung infection and suppression of Th17-mediated neutrophil recruitment in exogenous SOCS3 transfer in vitro. Mol. Med. Rep. 16: 778-786.
50. Ding, F. M., X. Y. Zhang, Y. Q. Chen, R. M. Liao, G. G. Xie, P. Y. Zhang, P. Shao, and M. Zhang. 2018. Lentivirus-mediated overexpression of suppressor of cytokine signaling-3 reduces neutrophilic airway inflammation by suppressing T-helper 17 responses in mice with chronic Pseudomonas aeruginosa lung infections. Int. J. Mol. Med. 41: 2193-2200.
51. Tateda, K., T. A. Moore, J. C. Deng, M. W. Newstead, X. Zeng, A. Matsukawa, M. S. Swanson, K. Yamaguchi, and T. J. Standiford. 2001. Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia. J. Immunol. 166: 3355-3361.
52. Xu, N., X. P. Gao, R. D. Minshall, A. Rahman, and A. B. Malik. 2002. Timedependent reversal of sepsis-induced PMN uptake and lung vascular injury by expression of CD18 antagonist. Am. J. Physiol. Lung Cell. Mol. Physiol. 282: L796-L802.
53. Shenoy, V., Y. Qi, M. J. Katovich, and M. K. Raizada. 2011. ACE2, a promising therapeutic target for pulmonary hypertension. Curr. Opin. Pharmacol. 11: 150-155.
54. Dhawale, V. S., V. R. Amara, P. A. Karpe, V. Malek, D. Patel, and K. Tikoo. 2016. Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model. Toxicol. Appl. Pharmacol. 306: 17-26.
55. Gu, H., Z. Xie, T. Li, S. Zhang, C. Lai, P. Zhu, K. Wang, L. Han, Y. Duan, Z. Zhao, et al. 2016. Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus. Sci. Rep. 6: 19840.
56. Rathinasabapathy, A., A. J. Bryant, T. Suzuki, C. Moore, S. Shay, S. Gladson, J. D. West, and E. J. Carrier. 2018. rhACE2 therapy modifies bleomycininduced pulmonary hypertension via rescue of vascular remodeling. Front. Physiol. 9: 271.
57. Khan, A., C. Benthin, B. Zeno, T. E. Albertson, J. Boyd, J. D. Christie, R. Hall, G. Poirier, J. J. Ronco, M. Tidswell, et al. 2017. A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Crit. Care 21: 234.
58. Lambert, D. W., M. Yarski, F. J. Warner, P. Thornhill, E. T. Parkin, A. I. Smith, N. M. Hooper, and A. J. Turner. 2005. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2). J. Biol. Chem. 280: 30113-30119.
59. Park, H., Z. Li, X. O. Yang, S. H. Chang, R. Nurieva, Y. H.Wang, Y.Wang, L. Hood, Z. Zhu, Q. Tian, and C. Dong. 2005. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 6: 1133-1141.
60. Aujla, S. J., P. J. Dubin, and J. K. Kolls. 2007. Interleukin-17 in pulmonary host defense. Exp. Lung Res. 33: 507-518.
61. Li, P., Q. Z. Yang, W. Wang, G. Q. Zhang, and J. Yang. 2018. Increased IL-4-and IL-17-producing CD8+ cells are related to decreased CD39+CD4+Foxp3+ cells in allergic asthma. J. Asthma 55: 8-14.
62. Sun, L. D., S. Qiao, Y. Wang, G. J. Pang, X. Y. Zha, T. L. Liu, H. L. Zhao, J. Y. Liang, N. B. Zheng, L. Tan, et al. 2018. Vg4+ T cells: A novel IL-17-producing gd T subsets during the early phase of chlamydial airway infection in mice. Mediators Inflamm. 2018: 6265746.
63. Cai, T., J. Qiu, Y. Ji, W. Li, Z. Ding, C. Suo, J. Chang, J. Wang, R. He, Y. Qian, et al. 2019. IL-17-producing ST2+ group 2 innate lymphoid cells play a pathogenic role in lung inflammation. J. Allergy Clin. Immunol. 143: 229-244.e9.
64. Ruddy, M. J., F. Shen, J. B. Smith, A. Sharma, and S. L. Gaffen. 2004. Interleukin-17 regulates expression of the CXC chemokine LIX/CXCL5 in osteoblasts: Implications for inflammation and neutrophil recruitment. J. Leukoc. Biol. 76: 135-144.
65. Griffin, G. K., G. Newton, M. L. Tarrio, D. X. Bu, E. Maganto-Garcia, V. Azcutia, P. Alcaide, N. Grabie, F. W. Luscinskas, K. J. Croce, and A. H. Lichtman. 2012. IL-17 and TNF-a sustain neutrophil recruitment during inflammation through synergistic effects on endothelial activation. J. Immunol. 188: 6287-6299.
66. Yuan, S., S. Zhang, Y. Zhuang, H. Zhang, J. Bai, and Q. Hou. 2015. Interleukin-17 stimulates STAT3-mediated endothelial cell activation for neutrophil recruitment. Cell. Physiol. Biochem. 36: 2340-2356.
67. Veres, T. Z., T. Kopcsányi, N. van Panhuys, M. Y. Gerner, Z. Liu, P. Rantakari, J. Dunkel, M. Miyasaka, M. Salmi, S. Jalkanen, and R. N. Germain. 2017. Allergen-induced CD4+ T cell cytokine production within airway mucosal dendritic cell-T cell clusters drives the local recruitment of myeloid effector cells. J. Immunol. 198: 895-907.
68. Zhu, H., J. Li, S. Wang, K. Liu, L. Wang, and L. Huang. 2013. Hmgb1-TLR4-IL-23-IL-17A axis promote ischemia-reperfusion injury in a cardiac transplantation model. Transplantation 95: 1448-1454.
69. Laan, M., Z. H. Cui, H. Hoshino, J. Lötvall, M. Sjöstrand, D. C. Gruenert, B. E. Skoogh, and A. Lindén. 1999. Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways. J. Immunol. 162: 2347-2352.
70. Lindén, A. 2001. Role of interleukin-17 and the neutrophil in asthma. Int. Arch. Allergy Immunol. 126: 179-184.
71. Nishihara, M., H. Ogura, N. Ueda, M. Tsuruoka, C. Kitabayashi, F. Tsuji, H. Aono, K. Ishihara, E. Huseby, U. A. Betz, et al. 2007. IL-6-gp130-STAT3 in T cells directs the development of IL-17+ Th with a minimum effect on that of Treg in the steady state. Int. Immunol. 19: 695-702.
72. Wilson, R. P., M. L. Ives, G. Rao, A. Lau, K. Payne, M. Kobayashi, P. D. Arkwright, J. Peake, M. Wong, S. Adelstein, et al. 2015. STAT3 is a critical cell-intrinsic regulator of human unconventional T cell numbers and function. J. Exp. Med. 212: 855-864.
73. Su, S. A., D. Yang, W. Zhu, Z. Cai, N. Zhang, L. Zhao, J. A. Wang, and M. Xiang. 2016. Interleukin-17A mediates cardiomyocyte apoptosis through Stat3-iNOS pathway. Biochim. Biophys. Acta 1863: 2784-2794.
74. Ma, M., W. Huang, and D. Kong. 2018. IL-17 inhibits the accumulation of myeloid-derived suppressor cells in breast cancer via activating STAT3. Int. Immunopharmacol. 59: 148-156.
75. Williamson, L., I. Ayalon, H. Shen, and J. Kaplan. 2019. Hepatic STAT3 inhibition amplifies the inflammatory response in obese mice during sepsis. Am. J. Physiol. Endocrinol. Metab. 316: E286-E292.