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We recently showed that IL-2 and IL-33, especially as a hybrid cytokine (IL233 - bearing IL-2 and IL-33 activities in one molecule), potentiated Tregs and group 2 innate lymphoid cells (ILC2) to prevent renal injury. Recent studies have indicated a reparative function for Tregs and ILC2. Here, using doxorubicin-induced nephrotoxic renal injury\u00a0model, we investigated whether IL233 administration either before, late or very late after renal injury can restore kidney structure and function. We found that IL233 treatment even 2-weeks post-doxorubicin completely restored kidney function accompanied with an increase Treg and ILC2 in lymphoid and renal compartments, augmented anti-inflammatory cytokines and attenuated proinflammatory cytokine levels. IL233 treated mice had reduced inflammation, kidney injury (Score values - saline: 3.34\u2009\u00b1\u20090.334; IL233 pre: 0.42\u2009\u00b1\u20090.162; IL233 24\u2009hrs: 1.34\u2009\u00b1\u20090.43; IL233 1 week: 1.2\u2009\u00b1\u20090.41; IL233 2 week: 0.47\u2009\u00b1\u20090.37; IL233 24\u2009hrs\u2009+\u2009PC61: 3.5\u2009\u00b1\u20090.74) and fibrosis in all treatment regimen as compared to saline controls. Importantly, mice treated with IL233 displayed a reparative program in the kidneys, as evidenced by increased expression of genes for renal progenitor-cells and nephron segments. Our findings present the first evidence of an immunoregulatory cytokine, IL233, which could be a potent therapeutic strategy that augments Treg and ILC2 to not only inhibit renal injury, but also promote regeneration.<\/jats:p>","DOI":"10.1038\/s41598-019-39886-9","type":"journal-article","created":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T06:06:43Z","timestamp":1551420403000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["A Novel Hybrid Cytokine IL233 Mediates regeneration following Doxorubicin-Induced Nephrotoxic Injury"],"prefix":"10.1038","volume":"9","author":[{"given":"Vikram","family":"Sabapathy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nardos Tesfaye","family":"Cheru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Corey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh","family":"Mohammad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,1]]},"reference":[{"key":"39886_CR1","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1146\/annurev-med-050214-013407","volume":"67","author":"A Zuk","year":"2016","unstructured":"Zuk, A. & Bonventre, J. 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