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Nonetheless, the long\u2010term immune consequences of paediatric sepsis are indeterminate. We sought to investigate the role of age in the genesis of immunosuppression following sepsis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Here, we compared the frequency of Tregs, the activation of the IL\u201033\/ILC2s axis in M2 macrophages and the DNA methylation of epithelial lung cells from post\u2010septic infant and adult mice. Likewise, sepsis\u2010surviving mice were inoculated intranasally with <jats:styled-content style=\"fixed-case\"><jats:italic>Pseudomonas aeruginosa<\/jats:italic><\/jats:styled-content> or by subcutaneous inoculation of the B16 melanoma cell line. Finally, blood samples from sepsis\u2010surviving patients were collected and the concentration of IL\u201033 and Tregs frequency were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In contrast to 6\u2010week\u2010old mice, 2\u2010week\u2010old mice were resistant to secondary infection and did not show impairment in tumour controls upon melanoma challenge. Mechanistically, increased IL\u201033 levels, Tregs expansion, and activation of ILC2s and M2\u2010macrophages were observed in 6\u2010week\u2010old but not 2\u2010week\u2010old post\u2010septic mice. Moreover, impaired IL\u201033 production in 2\u2010week\u2010old post\u2010septic mice was associated with increased DNA methylation in lung epithelial cells. Notably, IL\u201033 treatment boosted the expansion of Tregs and induced immunosuppression in 2\u2010week\u2010old mice. Clinically, adults but not paediatric post\u2010septic patients exhibited higher counts of Tregs and seral IL\u201033 levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>These findings demonstrate a crucial and age\u2010dependent role for IL\u201033 in post\u2010sepsis immunosuppression. Thus, a better understanding of this process may lead to differential treatments for adult and paediatric sepsis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16286","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:51Z","timestamp":1700784051000},"page":"1308-1323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Paediatric sepsis survivors are resistant to sepsis\u2010induced long\u2010term immune dysfunction"],"prefix":"10.1111","volume":"181","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6911-4765","authenticated-orcid":false,"given":"David F.","family":"Col\u00f3n","sequence":"first","affiliation":[{"name":"Center of Research in Inflammatory Diseases (CRID) University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"},{"name":"Departments of Biochemistry and Immunology University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2100-9963","authenticated-orcid":false,"given":"Carlos W.","family":"Wanderley","sequence":"additional","affiliation":[{"name":"Center of Research in Inflammatory Diseases (CRID) University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"},{"name":"Department of Pharmacology University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter M.","family":"Turato","sequence":"additional","affiliation":[{"name":"Center of Research in Inflammatory Diseases (CRID) University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa F.","family":"Borges","sequence":"additional","affiliation":[{"name":"Center of Research in Inflammatory Diseases (CRID) University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"},{"name":"Department of Pharmacology University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5613-2756","authenticated-orcid":false,"given":"Marcelo","family":"Franchin","sequence":"additional","affiliation":[{"name":"School of Dentistry Alfenas Federal University  Alfenas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda V. 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