Fractalkine (CX3CL1) as an amplification circuit of polarized Th1 responses
Paolo Fraticelli, … , Annunciata Vecchi, Alberto Mantovani
Paolo Fraticelli, … , Annunciata Vecchi, Alberto Mantovani
Published May 1, 2001
Citation Information: J Clin Invest. 2001;107(9):1173-1181. https://doi.org/10.1172/JCI11517.
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Article

Fractalkine (CX3CL1) as an amplification circuit of polarized Th1 responses

Abstract

Fractalkine (FKN, CX3CL1) is a membrane-bound CX3C chemokine induced by primary proinflammatory signals in vascular endothelial cells (ECs). Here we examined the role of FKN in polarized Th1 or Th2 responses. Proinflammatory signals, including LPS, IL-1, TNF, and CD40 ligand, induced FKN, as did IFN-γ, which had synergistic activity with TNF. IL-4 and IL-13 did not stimulate the expression of FKN and markedly reduced induction by TNF and IFN-γ. TNF alone or combined with IFN-γ also induced release of soluble FKN, which was inhibited by IL-4 and IL-13. In light of this differential regulation of FKN by the master cytokines that control polarized responses, we analyzed the interaction of FKN with natural killer (NK) cells and polarized T-cell populations. NK cells expressed high levels of the FKN receptor CX3CR1 and responded to FKN. CX3CR1 was preferentially expressed in Th1 compared with Th2 cells. Th1 but not Th2 cells responded to FKN. By immunohistochemistry, FKN was expressed on ECs in psoriasis, a Th1-dominated skin disorder, but not in Th2-driven atopic dermatitis. Similarly, ECs in Mycobacterium tuberculosis granulomatous lymphadenitis, but not those in reactive lymph node hyperplasia or in Castelman’s disease, showed immunoreactive FKN. These results indicate that regulated expression of FKN in ECs participates in an amplification circuit of polarized type I responses.

Authors

Paolo Fraticelli, Marina Sironi, Giancarlo Bianchi, Daniele D’Ambrosio, Cristina Albanesi, Antonella Stoppacciaro, Marcello Chieppa, Paola Allavena, Luigi Ruco, Giampiero Girolomoni, Francesco Sinigaglia, Annunciata Vecchi, Alberto Mantovani

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FKN and CX3CR1 immunostaining in M. tuberculosis granulomatous lymphaden...
FKN and CX3CR1 immunostaining in M. tuberculosis granulomatous lymphadenitis. (a) Anti-FKN immunostaining is confined to blood vessels and to a few scattered large dendritic-like cells of the paracortex. A faint staining is present also in scattered macrophages close to the necrotic area of the granuloma. (b) Double staining with CD34 (brown) shows that FKN (blue) is expressed by the ECs of a large number of paracortical vessels. (c) The large dendritic-like FKN-positive cells (blue) scattered in the paracortex were shown to be CD1a-positive (brown), newly migrated immature dendritic cells. (d) The positivity for CX3CR1 is present in the epithelioid macrophages of the granuloma and in cells with macrophage-like morphology and some lymphocyte-like cells in the paracortex. Double stained sections were not counterstained. (a, b, and d) ×250; (c) ×400.