title: The cell-to-cell coordination between activated T cells and CpG-stimulated macrophages synergistically induce elevated levels of IL-10 via NF-κB1, STAT3, and CD40/CD154.
abstract: BACKGROUND
  Studies into the regulation of interleukin-10 (IL-10), have focused only on the molecular or single-cell level. The cues that induce IL-10 in the context of cell-to-cell communication are scarce. To fill this gap, this study elucidates the cell-to-cell interaction dependent regulation of IL-10.
  
  
  RESULTS
  The simultaneous activation of CD4+ T cells via CD3/CD28 and stimulation of macrophages via CpG and their intercellular communication with each other in the same microenvironment is necessary to induce a synergistic expression of IL-10. NF-κB1, ERK, and STAT3 are positive regulators of this cell-to-cell communication mediated molecular change of IL-10 induction. Strikingly, the activation of CD40/CD154 signaling is a negative regulator of IL-10 levels by CD3/CD28/CpG.
  
  
  CONCLUSIONS
  These findings are of prominence as CD3/CD28/CpG treatment can induce the anti-inflammatory cytokines IL-10 and IL-30, and the activation or inhibition of the CD40/CD154 acts as molecular rheostat of the expression of IL-10 or IL-30. More importantly, this not only serves as an example of IL-10 regulation at the cellular via coordination of two signals from two cell types, but these findings also lay the molecular and cellular groundwork for future studies to investigate how to manipulate IL-10 or IL-30 production during inflammation, cancer, or autoimmune diseases.
authors: Denada
authors: D
authors: Dibra
authors: Department of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd,, Houston, TX 77030, USA. sli4@mdanderson.org.
authors: Shulin
authors: S
authors: Li
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D002450:Cell Communication; D018899:CpG Islands; D016753:Interleukin-10 / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D019013:CD40 Antigens; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D016753:Interleukin-10; D023201:CD40 Ligand