Evidence for a cross-talk between human neutrophils and Th17 cells

Abstract

Interleukin-17A (IL-17A) and IL-17F are 2 of several cytokines produced by T helper 17 cells (Th17), which are able to indirectly induce the recruitment of neutrophils. Recently, human Th17 cells have been phenotypically characterized and shown to express discrete chemokine receptors, including CCR2 and CCR6. Herein, we show that highly purified neutrophils cultured with interferon-␥ plus lipopolysaccharide produce the CCL2 and CCL20 chemokines, the known ligands of CCR2 and CCR6, respectively. Accordingly, supernatants from activated neutrophils induced chemotaxis of Th17 cells, which was greatly suppressed by anti-CCL20 and anti-CCL2 antibodies. We also discovered that activated Th17 cells could directly chemoattract neutrophils via the release of biologically active CXCL8. Consistent with this reciprocal recruitment, neutrophils and Th17 cells were found in gut tissue from Crohn disease and synovial fluid from rheumatoid arthritis patients. Finally, we report that, although human Th17 cells can directly interact with freshly isolated or preactivated neutrophils via granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-␣, and interferon-␥ release, these latter cells cannot be activated by IL-17A and IL-17F, because of their lack of IL-17RC expression. Collectively, our results reveal a novel chemokine-dependent reciprocal cross-talk between neutrophils and Th17 cells, which may represent a useful target for the treatment of chronic inflammatory diseases. (Blood. 2010;115:335-343)

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

“…Proinflammatory N1 neutrophils have also been shown to promote CD8 + T cells recruitment and activation by producing T cell-attracting chemokines (e.g., CCL3, CXCL9, and CXCL10) and proinflammatory cytokines (e.g., IL-12, TNFα, GM-CSF, and VEGF) [61]. There is a mutual interplay between neutrophils and CD4 + T helper 17 cells (Th17) [62]. While IL-17 and CXCL8 secreted by Th17 cells induce the recruitment of neutrophils, secretion of CCL2 and CCL20 by activated neutrophils attracts Th17 cells [61][62][63].…”

“…While IL-17 and CXCL8 secreted by Th17 cells induce the recruitment of neutrophils, secretion of CCL2 and CCL20 by activated neutrophils attracts Th17 cells [61][62][63]. Th17 cells may further modulate neutrophil activity through secretion of TNFα, IFNγ and GM-CSF [62].…”

Th17 cells: new players in asthma pathogenesis

“…Both IL-17A and IL-17F can exist either as IL-17A and IL-17F homodimers or IL-17A-IL-17F heterodimers. The main role of Th17 cells is their ability to recruit and activate neutrophil granulocytes, either directly through IL-8 production (8) or indirectly by inducing the production of colony stimulatory factors (CSF) and CXCL8 (9) by tissue resident cells. More-over, Th17 lymphocytes are also able to stimulate the production of CXCL chemokines and mucins, MUC5AC and MUC5B, in primary human bronchial epithelial cells in vitro (10), and the expression of human beta defensin-2 (11) and CCL20 in lung epithelial cells (12).…”

Secretion of pro‐inflammatory cytokines and chemokines and loss of regulatory signals by fibroblast‐like synoviocytes in juvenile idiopathic arthritis

“…CXCL12 was increased in JIA FLS, but is reportedly decreased in RA synovial tissue 23, suggesting differences in pathways utilized for cell trafficking. CXCL8 has been observed in RA synovial tissue 23, but specifically in many cell types from the RA joint, including dendritic cells, synovial macrophages, neutrophils, and synovial fibroblasts 23, 24, 25, 26, 27, 28, in addition to synovial fluid of JIA 21, but had the largest fold‐change decrease in expression in cultured JIA FLS. When tested on synovial fluid there was no significant difference in expression, suggesting that there are likely other cell sources of CXCL8 in JIA as well.…”