Blocking of LFA-1 enhances expansion of Th17 cells induced by human CD14(+) CD16(++) nonclassical monocytes.

Traunecker, Emmanuel; Gardner, Rui; Fonseca, João Eurico; Polido-Pereira, Joaquim; Seitz, Michael; Villiger, Peter; Iezzi, Giandomenica; Padovan, Elisabetta (2015). Blocking of LFA-1 enhances expansion of Th17 cells induced by human CD14(+) CD16(++) nonclassical monocytes. European journal of immunology, 45(5), pp. 1414-1425. Wiley-VCH 10.1002/eji.201445100

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Among human peripheral blood (PB) monocyte (Mo) subsets, the classical CD14(++) CD16(-) (cMo) and intermediate CD14(++) CD16(+) (iMo) Mos are known to activate pathogenic Th17 responses, whereas the impact of nonclassical CD14(+) CD16(++) Mo (nMo) on T-cell activation has been largely neglected. The aim of this study was to obtain new mechanistic insights on the capacity of Mo subsets from healthy donors (HDs) to activate IL-17(+) T-cell responses in vitro, and assess whether this function was maintained or lost in states of chronic inflammation. When cocultured with autologous CD4(+) T cells in the absence of TLR-2/NOD2 agonists, PB nMos from HDs were more efficient stimulators of IL-17-producing T cells, as compared to cMo. These results could not be explained by differences in Mo lifespan and cytokine profiles. Notably, however, the blocking of LFA-1/ICAM-1 interaction resulted in a significant increase in the percentage of IL-17(+) T cells expanded in nMo/T-cell cocultures. As compared to HD, PB Mo subsets of patients with rheumatoid arthritis were hampered in their T-cell stimulatory capacity. Our new insights highlight the role of Mo subsets in modulating inflammatory T-cell responses and suggest that nMo could become a critical therapeutic target against IL-17-mediated inflammatory diseases.

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