{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T13:03:24Z","timestamp":1785675804094,"version":"3.56.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"43","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Harvard society of fellow","award":["Junior Fellowship"],"award-info":[{"award-number":["Junior Fellowship"]}]},{"DOI":"10.13039\/100008730","name":"The Norwegian Cancer Society","doi-asserted-by":"crossref","award":["Project 198164"],"award-info":[{"award-number":["Project 198164"]}],"id":[{"id":"10.13039\/100008730","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH Director&apos;s Pioneer Award","award":["1DP1AI150593-01"],"award-info":[{"award-number":["1DP1AI150593-01"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,10,25]]},"abstract":"<jats:p>\n                    The distribution of Ly6C\/G-positive cells in response to an infection of the mouse respiratory tract with influenza A virus was followed noninvasively over time by immuno-positron emission tomography. We converted nanobodies that recognize Ly6C and Ly6G, markers of neutrophils and other myeloid cells, as well as an influenza hemagglutinin\u2013specific nanobody, into\n                    <jats:sup>89<\/jats:sup>\n                    Zr-labeled PEGylated positron emission tomography (PET) imaging agents. The PET images showed strong accumulation of these imaging agents in the lungs of infected mice. Immunohistochemistry of influenza virus\u2013infected mice and control mice, injected with a biotinylated and PEGylated version of the Ly6C\/G-specific nanobody, showed the presence of abundant Ly6C\/G-positive myeloid cells and positivity for Ly6C\/G on bronchial epithelium in influenza virus\u2013infected mice. This is consistent with focal inflammation in the lungs, a finding that correlated well with the immuno-PET results. No such signals were detected in control mice. Having shown by PET the accumulation of the Ly6C\/G-specific nanobody in infected lungs, we synthesized conjugates of Ly6C\/G-specific nanobodies with dexamethasone to enable targeted delivery of this immunosuppressive corticosteroid to sites of inflammation. Such conjugates reduced the weight loss that accompanies infection, while the equivalent amount of free dexamethasone was without effect. Nanobody-drug conjugates thus enable delivery of drugs to particular cell types at the appropriate anatomic site(s). By avoiding systemic exposure to free dexamethasone, this strategy minimizes its undesirable side effects because of the much lower effective dose of the nanobody-dexamethasone conjugate. The ability to selectively target inflammatory cells may find application in the treatment of other infections or other immune-mediated diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2211065119","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T15:10:57Z","timestamp":1666019457000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":18,"title":["Targeted delivery of an anti-inflammatory corticosteroid to Ly6C\/G-positive cells abates severity of influenza A symptoms"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8124-1265","authenticated-orcid":false,"given":"Novalia","family":"Pishesha","sequence":"first","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115"},{"name":"Society of Fellows, Harvard University, Cambridge, MA 02138"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault","family":"Harmand","sequence":"additional","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Carpenet","sequence":"additional","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atul","family":"Bhan","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraful","family":"Islam","sequence":"additional","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate","family":"van den Doel","sequence":"additional","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"William","family":"Pinney","sequence":"additional","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1090-6071","authenticated-orcid":false,"given":"Hidde L.","family":"Ploegh","sequence":"additional","affiliation":[{"name":"Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00059-020-04923-1"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-76781-0"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00805-z"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2020.09.001"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-06292-z"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.00420"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.572009"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200652"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21648"},{"key":"e_1_3_4_10_2","first-page":"CD007720","article-title":"Corticosteroids for pneumonia","volume":"12","author":"Stern A.","year":"2017","unstructured":"A. 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