Gene expressions of lipopolysaccharide receptors, toll-like receptors 2 and 4, are differently regulated in mouse T lymphocytes

Abstract

Toll-like receptors (TLRs) are a family of mammalian proteins homologous to Drosophila Toll. Human TLR2 was shown to mediate the responsiveness to lipopolysaccharide (LPS). On the other hand, gene mutations of mouse TLR4 (mTLR4) in LPS-hyporesponsive strains have suggested that mTLR4 is essential for LPS-signaling in mice, but the role of mTLR2 has not been explored. This report describes molecular cloning of the mTLR2 cDNA. Overexpression of mTLR2 and mouse CD14 conferred LPS-inducibility of c-Jun N-terminal kinase phosphorylation and nuclear factor-κB activation to COS7 cells, suggesting that mTLR2 is a signaling receptor for LPS. BothmTLR2 and mTLR4 genes were expressed in T cells. Treatment with anti-CD3ɛ, PMA plus ionomycin, or interleukin-2 (IL-2)/IL-15 increased mTLR2 but not mTLR4 messenger RNA (mRNA) in some T cell lines. Specific inhibitors of mitogen-activated extracellular signal-regulated kinase and fusion protein 38 (p38) kinase inhibited mTLR2 mRNA up-regulation by PMA plus ionomycin. This suggests that extracellular signal-regulated kinase and p38 kinase pathways were involved. Additionally, LPS treatment of EL-4 cell line decreasedIL-4 gene expression. Our results indicate that both mTLR2 and mTLR4 are involved in LPS signaling, but their expressions are regulated differently in T cells, and that LPS may directly affect T-cell functions by binding to TLRs.

Phenotypic differences of CD4+ T cells in response to red blood cell immunization in transfused sickle cell disease patients

“…The promotion of Th cells is directly dependent on TLR signaling [21], and activation of TLR3 or TLR9 in mouse models can boost the allogeneic immune responses against RBC antigens [6,16]. TCR activation is enhanced by TLR2 expression [18]; the lower TLR2 expression on CD4 + T cells in nonalloimmunized SCD patients suggests that the sensitivity to TCR activation is lower in nonresponder patients. Moreover, TLR2 signaling in CD4 + T cells can promote the Th17 response [20], so the lower TLR2 expression may also suggest diminished B-cell helper function consistent with the nonresponder status of the patients.…”

“…Activation of TLR3 or TLR9 can enhance the allogeneic immune responses against RBC antigens in mouse [6,16]. Because of the underlying inflammatory state in SCD, TLR signaling may be central to alloimmunization, but it is not known whether TLR ligands can directly promote T-cell function in patients [17][18][19][20] or enhance T CD4 + activation [17,21,22].…”

LPS‐induced chemokine expression in both MyD88‐dependent and ‐independent manners is regulated by Cot/Tpl2‐ERK axis in macrophages

“…Thioglycollate-elicited peritoneal macrophages (TEPMs) were isolated from C57BL/6 and cot/tpl2 À/À mice as previously described [16] with minor modifications. Briefly, [8][9][10][11][12][13][14][15] week old age-matched male mice were injected intraperitoneally with 2.5 ml of 5% thioglycollate broth (Sigma-Aldrich, St. Louis, MO). Three days later, their peritoneal cavities were washed with 5 ml of cold PBS to collect TEPMs.…”

Effects of Toll-Like Receptor Signals in T-Cell Neoplasms

“…Leukemic cells from ATLL patients have been shown to proliferate in response to IL-2 [48,75,76]. The engagement of various TLRs on healthy T cells can enhance production of cytokines, which augment cell division (Table 1) [11,19,29,77]. Furthermore, the activation of TLR signals in T cells increases the expression levels of cytokine receptors (i.e., CD25 and CD132) on the T-cell surface and prolongs the duration of the receptor expression.…”