{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:06:00Z","timestamp":1781103960040,"version":"3.54.1"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,3,29]]},"abstract":"<jats:p>\n                    <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                    is commonly associated with allergic bronchopulmonary aspergillosis in patients with severe asthma in which chronic airway neutrophilia predicts a poor outcome. We were able to recapitulate fungus-induced neutrophilic airway inflammation in a mouse model in our efforts to understand the underlying mechanisms. However, neutrophilia occurred in a mouse strain-selective fashion, providing us with an opportunity to perform a comparative study to elucidate the mechanisms involved. Here we show that TNF-\u03b1, largely produced by Ly6c\n                    <jats:sup>+<\/jats:sup>\n                    CD11b\n                    <jats:sup>+<\/jats:sup>\n                    dendritic cells (DCs), plays a central role in promoting IL-17A from CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and collaborating with it to induce airway neutrophilia. Compared with C57BL\/6 mice, BALB\/c mice displayed significantly more TNF-\u03b1\u2013producing DCs and macrophages in the lung. Lung TNF-\u03b1 levels were drastically reduced in CD11c-DTR BALB\/c mice depleted of CD11c+ cells, and TNF-\u03b1\u2013producing Ly6c\n                    <jats:sup>+<\/jats:sup>\n                    CD11b\n                    <jats:sup>+<\/jats:sup>\n                    cells were abolished in Dectin-1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and MyD88\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    BALB\/c mice. TNF-\u03b1 deficiency itself blunted accumulation of inflammatory Ly6c\n                    <jats:sup>+<\/jats:sup>\n                    CD11b\n                    <jats:sup>+<\/jats:sup>\n                    DCs. Also, lack of TNF-\u03b1 decreased IL-17A but promoted IL-5 levels, switching inflammation from a neutrophil to eosinophil bias resembling that in C57BL\/6 mice. The TNF-\u03b1\n                    <jats:sup>low<\/jats:sup>\n                    DCs in C57BL\/6 mice contained more NF-\u03baB p50 homodimers, which are strong repressors of TNF-\u03b1 transcription. Functionally, collaboration between TNF-\u03b1 and IL-17A triggered significantly higher levels of the neutrophil chemoattractants keratinocyte cytokine and macrophage inflammatory protein 2 in BALB\/c mice. Our study identifies TNF-\u03b1 as a molecular switch that orchestrates a sequence of events in DCs and CD4 T cells that promote neutrophilic airway inflammation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1015476108","type":"journal-article","created":{"date-parts":[[2011,3,15]],"date-time":"2011-03-15T16:49:42Z","timestamp":1300207782000},"page":"5360-5365","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":113,"title":["TNF-\u03b1 from inflammatory dendritic cells (DCs) regulates lung IL-17A\/IL-5 levels and neutrophilia versus eosinophilia during persistent fungal infection"],"prefix":"10.1073","volume":"108","author":[{"given":"Mingjian","family":"Fei","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and"},{"name":"Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikha","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy B.","family":"Oriss","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manohar","family":"Yarlagadda","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupriya","family":"Khare","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuo","family":"Akira","sequence":"additional","affiliation":[{"name":"Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Osaka 565-0871, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinobu","family":"Saijo","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Iwakura","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A.","family":"Fallert Junecko","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd A.","family":"Reinhart","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oded","family":"Foreman","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Sacramento, CA 95838; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabir","family":"Ray","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and"},{"name":"Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Kolls","sequence":"additional","affiliation":[{"name":"Departments of Genetics and 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