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This study aimed to investigate the role of immune checkpoint molecules and regulatory cytokines in relation to disease severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A prospective cohort of 151 pediatric patients aged 1 month to 2 years was enrolled and classified into control, mild, moderate, and severe bronchiolitis groups. Immune checkpoint molecules (CTLA-4, TIM-3, TIGIT, GARP) and cytokines (IL-2R\u03b1, 4-1BB, TGF-\u03b21, LAG-3, galectin-9) were evaluated in CD4\u2009\n                      <jats:sup>+<\/jats:sup>\n                      \u2009FOXP3\n                      <jats:sup>+<\/jats:sup>\n                      (Treg) and CD4\u2009\n                      <jats:sup>+<\/jats:sup>\n                      \u2009FOXP3\n                      <jats:sup>\u2212<\/jats:sup>\n                      T cells, and in plasma using flow cytometry and ELISA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell levels decreased with increasing disease severity. Treg frequencies were elevated in mild cases but decreased in moderate and severe cases. CTLA-4 and TIM-3 expression increased on both Treg and non-Treg CD4\n                      <jats:sup>+<\/jats:sup>\n                      \u2009T cells in moderate and severe groups. Soluble PD-1, TIM-3, LAG-3, TGF-\u03b21, and 4-1BB levels were significantly elevated in severe bronchiolitis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Disease severity in bronchiolitis is associated with immune checkpoint dysregulation and an immunosuppressive environment. The observed alterations in T cell subsets and increased expression of CTLA-4 and TIM-3 highlight the potential of these molecules as biomarkers of disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>This study demonstrates that the severity of pediatric bronchiolitis is associated with the dysregulation of immune checkpoint molecules.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>It adds novel insight into the immunopathogenesis of bronchiolitis by focusing on early immune biomarkers beyond conventional inflammatory parameters.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These findings may support risk stratification and contribute to the development of targeted therapies in future pediatric bronchiolitis management.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-026-04853-4","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:26:53Z","timestamp":1773448013000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pediatric bronchiolitis disease severity is associated with immune checkpoint dysregulation"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3042-7999","authenticated-orcid":false,"given":"Mehmet Akif","family":"Dundar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2255-1685","authenticated-orcid":false,"given":"Serife","family":"Erdem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8470-4907","authenticated-orcid":false,"given":"Benhur","family":"Cetin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5816-0686","authenticated-orcid":false,"given":"Ahmet","family":"Eken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2691-4826","authenticated-orcid":false,"given":"Ekrem","family":"Unal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0702-6313","authenticated-orcid":false,"given":"Turan","family":"Guzel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2195-3551","authenticated-orcid":false,"given":"Yilmaz","family":"Secilmis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1168-3228","authenticated-orcid":false,"given":"Meda","family":"Kondolot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2934-7501","authenticated-orcid":false,"given":"Seyma","family":"Maras","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2047-2967","authenticated-orcid":false,"given":"Busra Seniz","family":"Demir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8287-7073","authenticated-orcid":false,"given":"Mohammad Ahmad","family":"Houran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3532-3277","authenticated-orcid":false,"given":"Mine","family":"Asan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8540-0625","authenticated-orcid":false,"given":"Basak Nur","family":"Akyildiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"4853_CR1","doi-asserted-by":"publisher","unstructured":"Astudillo, P. et al. 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