Heat shock protein 60 activates cytokine-associated negative regulator suppressor of cytokine signaling 3 in T cells: Effects on signaling, chemotaxis, and inflammation

Alexandra Zanin-Zhorov, Guy Tal, Shoham Shivtiel, Michal Cohen, Tsvee Lapidot, Gabriel Nussbaum, Raanan Margalit, Irun R. Cohen*, Ofer Lider

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Previously, we reported that treatment of T cells with the 60-kDa heat shock protein (HSP60) inhibits chemotaxis. We now report that treatment of purified human T cells with recombinant human HSP60 or its biologically active peptide p277 up-regulates suppressor of cytokine signaling (SOCS)3 expression via TLR2 and STAT3 activation. SOCS3, in turn, inhibits the downstream effects of stromal cell-derived-la (CXCL12)-CXCR4 interaction in: 1) phosphorylation of ERK1/2, Pyk2, AKT, and myosin L chain, required for cell adhesion and migration; 2) formation of rear-front T cell polarity; and 3) migration into the bone marrow of NOD/SCID mice. HSP60 also activates SOCS3 in mouse lymphocytes and inhibits their chemotaxis toward stromal cell-derived factor-1α and their ability to adoptively transfer delayed-type hypersensitivity. These effects of HSP60 could not be attributed to LPS or LPS-associated lipoprotein contamination. Thus, HSP60 can regulate T cell-mediated inflammation via specific signal transduction and SOCS3 activation.

Original languageAmerican English
Pages (from-to)276-285
Number of pages10
JournalJournal of Immunology
Volume175
Issue number1
DOIs
StatePublished - 1 Jul 2005
Externally publishedYes

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