Interleukin-14 Prevents Cytarabine or Irradiation Induced Neutropenia via JAK/STAT3 Signaling

Severe neutropenia significantly increases the risk of bacterial infections. Recent studies have shown that the cytokine interleukin 14 (IL-14) plays an important role in immune cells, but its potential role in neutropenia induced by cytarabine (ara-c) or irradiation is unclear. To investigate the r...

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Vydáno v:Iranian journal of immunology Ročník 22; číslo 2; s. 106
Hlavní autoři: Xu, Shengnan, Ye, Chaoqiong, Wu, Zhihua, Wen, Chuying, Huang, Wenhui, Deng, Cong, Hua, Jiaye, Xie, Wei, Xiao, Min
Médium: Journal Article
Jazyk:angličtina
Vydáno: Iran Shiraz Institute for Cancer Research 23.06.2025
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ISSN:1735-1383, 1735-367X, 1735-367X
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Shrnutí:Severe neutropenia significantly increases the risk of bacterial infections. Recent studies have shown that the cytokine interleukin 14 (IL-14) plays an important role in immune cells, but its potential role in neutropenia induced by cytarabine (ara-c) or irradiation is unclear. To investigate the role of IL-14 in ara-c or irradiation-induced neutropenia. Two neutropenia models were induced by ara-c or irradiation. Neutrophil count was confirmed through flow cytometry and routine blood tests. IL-14 was used to assess the impact on neutropenia. IL-14 expression was analyzed using qPCR, Western blotting and ELISA. A IL-14 receptor (IL-14R) knockout mice model was utilized to confirm the role of IL-14R/STAT3 signaling in vivo. The results indicated that IL-14 treatment promoted proliferation and increased neutrophil counts in both bone marrow and peripheral blood, while IL-14R knockout suppressed this process. Furthermore, the downstream molecule of IL-14R, STAT3, showed enhanced phosphorylation levels in the presence of IL-14. Finally, we explored the source of IL-14 in the bone marrow, and found that lymphocytes secreted the highest levels of IL-14. Serum levels of IL-14 were significantly reduced in patients after chemotherapy. These results indicate that IL-14 prevents ara-c or irradiation-induced neutropenia by regulating lymphocytes and activating the IL-14R/STAT3 pathway in neutrophils. This evidence suggests that IL-14 is a potent cytokine for treating ara-c or irradiation-induced neutropenia.
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ISSN:1735-1383
1735-367X
1735-367X
DOI:10.22034/iji.2025.105019.2925