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Chemokines as regulators of T cell response

CXCL10 (which is the ligand of the variant CXCR3-A) up-regulates the production of IFN-gamma and down-regulates the production of type 2 cytokines, whereas CXCL4 (the ligand of the new isophorm called CXCR3-B) down-regulates the production of IFN-gamma and up-regulates the production of IL-4, IL-5 and IL-13 in antigen or allergen-specific T cells.

CXCL10 and CXCL4 induce two different signalling pathways inside T cells. CXCL10 up-regulates the expression of T-bet and down-regulates GATA-3, whereas CXCL4 inhibites T-bet transcription and associates with increased GATA-3 expression. Finally, CXCL4 is able to induce the direct activation of IL-5 and IL-13 transcription.

These findings demonstrate that CXCL10 and CXCL4 exert opposite effects on the production of human Th1 and Th2 cytokines through their interaction with CXCR3-A or CXCR3-B and the subsequent activation of distinct signal transduction pathways, thus providing evidence for the existence of a novel internal regulatory model of Th1- and Th2-cell polarization.

CXCL10 can be a fruitful candidate as adjuvants of DNA vaccines for allergy.

Reported by

University of Firenze
Policlinico Careggi, Viale Morgagni, 85
50134 Firenze
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