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Human T H 17 cell development requires processing of dendritic cell-derived CXCL8 by neutrophil elastase
Ist Teil von
Journal of allergy and clinical immunology, 2018-06, Vol.141 (6), p.2286
Ort / Verlag
United States: Elsevier Limited
Erscheinungsjahr
2018
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
In line with this hypothesis, we found that patients with impaired neutrophil function (for details, see the Methods section in this article's Online Repository at www.jacionline.org) had no or severely decreased percentages of TH17 cells in their CD4+ memory T-cell compartment compared with healthy controls (Fig 1, A). [...]DCs activated by heat-killed C albicans hyphae were not able to induce the development of TH17 cells from highly pure healthy human CD4+CD45RA+CD45RO− naive T cells. [...]ligation of signal inhibitory receptor on leukocytes-1, which limits neutrophil extracellular trap (NET) formation,6 resulted in a strong inhibition of TH17 cell induction (Fig 2, C). Because these data suggested the involvement of soluble factors present in neutrophilic granules or attached to NETs, we further investigated the role of neutrophil elastase (NE). Importantly, rhCXCL8(72) but not rhCXCL8(77) strongly promoted TH17 cell development from naive T cells by C albicans–activated DCs without consistently affecting TH1 cell development (Fig 2, G). [...]reparixin (inhibitor of CXCL8Rs CXCR1 and CXCR2) inhibited TH17 cell formation (Fig 2, H). [...]CXCL8(77), which binds to the same receptor as CXCL8(72), dose dependently inhibited the induction of TH17 cells by CXCL8(72) (Fig 2, J), explaining why low levels of CXCL8(72) and abundance of CXCL8(77) produced by DCs in the absence of neutrophils was insufficient to drive TH17 cell development.