{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:43:32Z","timestamp":1787161412180,"version":"build-2736575974"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    \u03b1L\u03b22 (LFA-1) mediated interactions with ICAM-1 and ICAM-2 predominate leukocyte-vascular interactions, but their functions in extravascular cell-cell communications is still debated. The roles of these two ligands in leukocyte trafficking, lymphocyte differentiation, and immunity to influenza infections were dissected in the present study. Surprisingly, double ICAM-1 and ICAM-2 knock out mice (herein ICAM-1\/2\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice) infected with a lab adapted H1N1 influenza A virus fully recovered from infection, elicited potent humoral immunity, and generated normal long lasting anti-viral CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell memory. Furthermore, lung capillary ICAMs were dispensable for both NK and neutrophil entry to virus infected lungs. Mediastinal lymph nodes (MedLNs) of ICAM-1\/2\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice poorly recruited na\u00efve T cells and B lymphocytes but elicited normal humoral immunity critical for viral clearance and effective CD8\n                    <jats:sup>+<\/jats:sup>\n                    differentiation into IFN-\u03b3 producing T cells. Furthermore, whereas reduced numbers of virus specific effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells accumulated inside infected ICAM-1\/2\n                    <jats:sup>-\/-<\/jats:sup>\n                    lungs, normal virus-specific T\n                    <jats:sub>RM<\/jats:sub>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    cells were generated inside these lungs and fully protected ICAM-1\/2\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice from secondary heterosubtypic infections. B lymphocyte entry to the MedLNs and differentiation into extrafollicular plasmablasts, producing high affinity anti-influenza IgG2a antibodies, were also ICAM-1 and ICAM-2 independent. A potent antiviral humoral response was associated with accumulation of hyper-stimulated cDC2s in ICAM null MedLNs and higher numbers of virus-specific T follicular helper (Tfh) cells generated following lung infection. Mice selectively depleted of cDC ICAM-1 expression supported, however, normal CTL and Tfh differentiation following influenza infection, ruling out essential co-stimulatory functions of DC ICAM-1 in CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation. Collectively our findings suggest that lung ICAMs are dispensable for innate leukocyte trafficking to influenza infected lungs, for the generation of peri-epithelial T\n                    <jats:sub>RM<\/jats:sub>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    cells, and long term anti-viral cellular immunity. In lung draining LNs, although ICAMs promote lymphocyte homing, these key integrin ligands are not required for influenza-specific humoral immunity or generation of IFN-\u03b3 effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. In conclusion, our findings suggest unexpected compensatory mechanisms that orchestrate protective anti-influenza immunity in the absence of vascular and extravascular ICAMs.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.1041552","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T23:30:32Z","timestamp":1676935832000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["ICAMs are dispensable for influenza clearance and anti-viral humoral and cellular immunity"],"prefix":"10.3389","volume":"13","author":[{"given":"Stav","family":"Kozlovski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofer","family":"Regev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Sapoznikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Kizner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagit","family":"Achdout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Petrovich-Kopitman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Elkahal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoseph","family":"Addadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Vargas E.","family":"Silva Castanheira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara W.","family":"Feigelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Kubes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam","family":"Erez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalio","family":"Garbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronen","family":"Alon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2236","article-title":"Regulation of immunological homeostasis in the respiratory 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