title: Signaling via TLR2 and TLR4 Directly Down-Regulates T Cell Effector Functions: The Regulatory Face of Danger Signals.
abstract: Toll-like receptors (TLRs) are widely expressed and play an essential role in the activation of innate immune cells. However, certain TLRs are also expressed on T cells, and TLR ligands can directly modulate T cell functions. Here, we discuss findings indicating that T cells directly respond to Heat Shock Protein (HSP) 60, a self molecule, or to the HSP60-derived peptide, p277, via a TLR2-dependent mechanism. HSP60 has been considered to be a "danger signal" for the immune system because of its ability to induce pro-inflammatory phenotypes in innate immune cells - in this case via TLR4 activation; nevertheless, TLR2 engagement by HSP60 on T cells can lead to resolution of inflammation by up-regulating the suppression function of regulatory T cells and shifting the resulting cytokine secretion balance toward a Th2 phenotype. Moreover, T cell TLR4 engagement by LPS leads to up-regulation of suppressor of cytokine signaling 3 expression and consequently down-regulates T cell chemotaxis. Thus, TLR2 and TLR4 activation can contribute to both induction and termination of effector immune responses by controlling the activities of both innate and adaptive immune cells.
authors.affiliation: Kadmon Research Institute , New York, NY , USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zanin-Zhorov
authors.forename: Irun R
authors.initials: IR
authors.lastname: Cohen
keywords: HSP60; LPS; T cell inhibition; TLR2; TLR4; direct signaling; inflammation
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