title: CD4+Foxp3+ regulatory T-cell impairment by paclitaxel is independent of toll-like receptor 4.
abstract: Paclitaxel (PTX) is one of the most widely used clinical antitumour drugs in chemotherapy nowadays. Its effect on immune system has become a hot spot of research in recent years. Here, we demonstrated that PTX not only decreased the percentage of CD4+Foxp3+ regulatory T (Treg) cells both in vitro and in vivo but also impaired cell viability and cytokine production of Treg cells rather than CD4+Foxp3- effector T (Teff) cells. As PTX has been reported to mimic the activity of LPS to trigger the toll-like receptor 4 (TLR4) signalling pathway in macrophages, we investigated the possible role of TLR4 in the effect of PTX. However, although TLR4 expression on Treg cells was higher than that on Teff cells, the expression level remained unaltered in both Treg and Teff cells after PTX treatment. Surface molecules and activation markers in Treg and Teff cells did not change, either. Further study showed that the effect of PTX on TLR4-/- mice deficient in TLR4 signalling was similar to that on C57BL/6 mice both in vivo and in vitro. These data indicate that the selective impairment of Treg cells by PTX is independent of TLR4.
authors.affiliation: Department of Immunology of Shanghai Medical College and Key Laboratory of Molecular Medicine of Ministry of Education, Fudan Univesity, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: N
authors.initials: N
authors.lastname: Liu
authors.forename: S D
authors.initials: SD
authors.lastname: Xiong
authors.forename: Y J
authors.initials: YJ
authors.lastname: Zheng
authors.forename: Y W
authors.initials: YW
authors.lastname: Chu
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000276:immunology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D017239:Paclitaxel