Human TSLP and TLR3 ligands promote differentiation of Th17 cells with a central memory phenotype under Th2‐polarizing conditions

Tanaka, Junya; Watanabe, Norihiko; Kido, Masahiro; Saga, Kenichi; Akamatsu, Takuji; Nishio, Akiyoshi; Chiba, Tsutomu

doi:10.1111/j.1365-2222.2008.03151.x

Cited by 116 publications

(90 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Second, our data also strongly suggest that tumor cells and tumor environmental stromal cells provide not only soluble cytokines but also cell-cell contact signaling for (32,33). In addition, recent studies have also shown that activation of dendritic cells, monocytes, and PBMCs by TLR and Nod signaling can potentiate human Th17 cell differentiation and production (22)(23)(24). Our results showed that TLR and Nod2 signaling can increase MCP-1 and RANTES expression on tumor cells and tumor-derived fibroblasts that can promote the migration and trafficking of Th17 cells.…”

Section: Discussionmentioning

confidence: 59%

“…More recently, studies from three groups demonstrated that TGF-b is also required for human Th17 cell differentiation (19)(20)(21). In addition to the direct regulation of Th17 cells by cytokines, recent data have also shown that modulation of APCs, such as dendritic cells, through the triggering of TLRs and nucleotide oligomerization binding domain (Nod)2 receptor can promote the differentiation and production of human Th17 cells (22)(23)(24). Improved understanding of human Th17 cell regulation is essential for the development of novel therapeutic strategies for treatment of a variety of diseases.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Tumor Microenvironments Direct the Recruitment and Expansion of Human Th17 Cells

Su¹,

Ye²,

Hsueh

et al. 2009

The Journal of Immunology

293

227

View full text Add to dashboard Cite

Although Th17 cells play critical roles in the pathogenesis of many inflammatory and autoimmune diseases, their prevalence among tumor-infiltrating lymphocytes (TILs) and function in human tumor immunity remains largely unknown. We have recently demonstrated high percentages of Th17 cells in TILs from ovarian cancer patients, but the mechanisms of accumulation of these Th17 cells in the tumor microenvironment are still unclear. In this study, we further showed elevated Th17 cell populations in the TILs obtained from melanoma and breast and colon cancers, suggesting that development of tumor-infiltrating CD4+ Th17 cells may be a general feature in cancer patients. We then demonstrated that tumor microenvironmental RANTES and MCP-1 secreted by tumor cells and tumor-derived fibroblasts mediate the recruitment of Th17 cells. In addition to their recruitment, we found that tumor cells and tumor-derived fibroblasts produce a proinflammatory cytokine milieu as well as provide cell–cell contact engagement that facilitates the generation and expansion of Th17 cells. We also showed that inflammatory TLR and nucleotide oligomerization binding domain 2 signaling promote the attraction and generation of Th17 cells induced by tumor cells and tumor-derived fibroblasts. These results identify Th17 cells as an important component of human TILs, demonstrate mechanisms involved in the recruitment and regulation of Th17 cells in tumor microenvironments, and provide new insights relevant for the development of novel cancer immunotherapeutic approaches.

show abstract

Section: Discussionmentioning

confidence: 59%

mentioning

confidence: 99%

Tumor Microenvironments Direct the Recruitment and Expansion of Human Th17 Cells

Su¹,

Ye²,

Hsueh

et al. 2009

The Journal of Immunology

293

227

View full text Add to dashboard Cite

show abstract

“…Further proof of the concept that IL-17 is involved in the augmentation of autoimmune disorders is provided by the observation that IL-17-deficient mice develop experimental autoimmune encephalitis with profoundly attenuated severity (24). Several mechanisms have been described that promote the differentiation of Th17 cells through myeloid DCs, such as the induction of NOTCH signaling in DCs (25), stimulation of the nucleotide oligomerization domain 2 with muramyldipeptide (26), activation of DCs with thymic stromal lymphopoietin and TLR3 ligands (27), stimulation of DCs with schistosome eggs (28), or incubation of DCs with TLR2, TLR4, and TLR7 agonists (29)(30)(31).…”

mentioning

confidence: 99%

Human Plasmacytoid Dendritic Cells Support Th17 Cell Effector Function in Response to TLR7 Ligation

Peng

Oldenburg

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

Signals involved in the commitment of Th17 differentiation are of substantial interest for our understanding of antimicrobial defense mechanisms and autoimmune disorders. Various ways in which myeloid dendritic cells modulate Th17 differentiation have been identified. However, although plasmacytoid dendritic cells (PDCs) are regarded as important players in antiviral/antimicrobial host defense and autoimmune diseases, a putative modulatory role of PDCs in Th17 differentiation has not yet been elucidated in detail. We demonstrated that PDCs are capable of promoting Th17 differentiation in response to TLR7 stimulation. Further, both the differentiation of Th17 cells from naive T cells and the amplification of Th17 effector functions of memory T cells are promoted by PDCs after TLR7 activation. Our data are of strong clinical relevance because TLR7 activation in PDCs might represent one of the missing links between innate and adaptive immune mechanisms and contribute to the amplification of Th17-driven autoimmune disorders as well as viral host defense.

show abstract

“…Recent evidence suggests that the airway epithelium also plays an important role in the induction of allergic airway responses by the release of thymic stromal lymphopoietin (TSLP), an IL-7-like cytokine that has been shown to activate DCs to induce Th2-cell responses and to promote the differentiation of TH-17 cells [10][11][12].…”

Section: Pathophysiology Of Allergic Airways Diseasementioning

confidence: 99%

Biomarkers in asthma and allergic rhinitis

Diamant

Boot

Mantzouranis

et al. 2010

Pulmonary Pharmacology & Therapeutics

View full text Add to dashboard Cite

Human TSLP and TLR3 ligands promote differentiation of Th17 cells with a central memory phenotype under Th2‐polarizing conditions

Abstract: These results suggest that through DC activation, human TSLP and TLR3 ligands promote differentiation of Th17 cells with the central memory T cell phenotype under Th2-polarizing conditions.

Cited by 116 publications

References 44 publications

Tumor Microenvironments Direct the Recruitment and Expansion of Human Th17 Cells

Tumor Microenvironments Direct the Recruitment and Expansion of Human Th17 Cells

Human Plasmacytoid Dendritic Cells Support Th17 Cell Effector Function in Response to TLR7 Ligation

Biomarkers in asthma and allergic rhinitis

Contact Info

Product

Resources

About