CD27+TIM-1+ memory B cells promoted the development of Foxp3+ Tregs and were associated with better survival in acute respiratory distress syndrome
- 62 Downloads
Acute respiratory distress syndrome (ARDS) is a rapid onset life-threatening condition involving uncontrolled propagation of inflammatory responses. Here, we observed that ARDS patients that survived presented significantly higher frequencies of TIM-1+ B cells, especially the CD27+TIM-1+ B cells, than the ARDS patients who succumbed to the condition. We then found that using BCR/CD40 antigen-dependent stimulation or Staphylococcus aureus Cowan (SAC) antigen-independent stimulation, TIM-1+ B cells presented significantly higher IL-10 secretion and/or TGF-β1 secretion, with SAC stimulation being more effective. CD4+ T cells that incubated with TIM-1+ B cells presented significantly elevated IL-10 secretion, TGF-β1 secretion, and Foxp3 expression, than CD4+ T cells that incubated with TIM-1− B cells, suggesting TIM-1+ B cells promoted the in vitro development of Foxp3+ Treg cells. Interestingly, this TIM-1+ B cell-mediated promotion of Foxp3 expression was mostly dependent on TGF-β1 but not IL-10, since neutralization of TGF-β1, but not IL-10, resulted in the suppression of Foxp3 expression. We further showed that in TIM-1+ B cells, the CD27+ classical memory B cell subset demonstrated more regulatory potency than the CD27− subset. Together, our results suggested that the TIM-1+ B cells, especially those that expressed CD27, could promote Foxp3 expression. Their clinical efficacy in treating ARDS should be examined in in vivo experiments.
KeywordsTIM-1+ B cell Breg IL-10 ALI
Compliance with ethical standards
Following ethical approval by Anzhen Hospital ethics committee and receiving written informed consent, peripheral blood was collected form the patients after admission into the intensive care units.
Conflict of interest
The authors declare that they have no conflict of interest.
- 2.Ding Q, Yeung M, Camirand G, Zeng Q, Akiba H, Yagita H, et al. Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice. J Clin Invest. 2011;121(9):3645–56. https://doi.org/10.1172/JCI46274.CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Aravena O, Ferrier A, Menon M, Mauri C, Aguillón JC, Soto L, et al. TIM-1 defines a human regulatory B cell population that is altered in frequency and function in systemic sclerosis patients. Arthritis Res Ther. 2017;19(1):8. https://doi.org/10.1186/s13075-016-1213-9.CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Liu J, Zhan W, Kim CJ, Clayton K, Zhao H, Lee E, Cao JC, Ziegler B, Gregor A, Yue FY, Huibner S, MacParland S, Schwartz J, Song HH, Benko E, Gyenes G, Kovacs C, Kaul R, Ostrowski M IL-10-producing B cells are induced early in HIV-1 infection and suppress HIV-1-specific T cell responses. Unutmaz D, editor. PLoS One 2014;9:e89236, 2, DOI: https://doi.org/10.1371/journal.pone.0089236.
- 9.Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315(8):788–800. https://doi.org/10.1001/jama.2016.0291.CrossRefPubMedGoogle Scholar
- 12.Singer BD, Mock JR, Aggarwal NR, Garibaldi BT, Sidhaye VK, Florez MA, et al. Regulatory T cell DNA methyltransferase inhibition accelerates resolution of lung inflammation. Am J Respir Cell Mol Biol. 2015;52(5):641–52. https://doi.org/10.1165/rcmb.2014-0327OC.CrossRefPubMedPubMedCentralGoogle Scholar
- 13.D’Alessio FR, Tsushima K, Aggarwal NR, West EE, Willett MH, Britos MF, et al. CD4+CD25+Foxp3+ Tregs resolve experimental lung injury in mice and are present in humans with acute lung injury. J Clin Invest. 2009;119(10):2898–913. https://doi.org/10.1172/JCI36498.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Blair PA, Noreña LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR, et al. CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity. 2010;32(1):129–40. https://doi.org/10.1016/j.immuni.2009.11.009.CrossRefPubMedGoogle Scholar