ICOS is critical for T helper cell–mediated lung mucosal inflammatory responses

Gonzalo, José-Ángel; Tian, Jane; Delaney, Tracy; Corcoran, Justin; Rottman, James B.; Lora, José M.; Al-Garawi, Amal; Kroczek, Richard A.; Gutierrez‐Ramos, José Carlos; Coyle, Anthony J.

doi:10.1038/89739

Cited by 257 publications

(148 citation statements)

References 52 publications

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“…ICOS-deficient T cells exhibited defects in Th2 cytokine secretion, being selectively impaired in IL-4 but not IFN-␥ expression after in vitro differentiation or in vivo priming by protein antigen (5). In agreement with a role for ICOS in Th2 responses, IL-4-dependent IgE production was defective in asthma-contracting mice lacking ICOS (5) or in which ICOS signaling was neutralized (11,12). Recently, in vitro Th polarization experiments suggested that ICOS costimulated Th2 cell differentiation by an IL-4-driven mechanism involving NFATc1 and c-Maf (13).…”

Section: The Inducible Costimulator (Icos)supporting

confidence: 52%

T Helper Cell-specific Regulation of Inducible Costimulator Expression via Distinct Mechanisms Mediated by T-bet and GATA-3

Tan

Goh

Wong

et al. 2008

Journal of Biological Chemistry

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Inducible costimulator (ICOS) expression is critical for T cellmediated immunity. We showed previously that T cell receptor and CD28 coengagement up-regulate ICOS expression in activated T cells via the induction of NFATc2. Here, we examined the regulation of ICOS expression by Th-specific transcription factors T-bet and GATA-3. Overexpression of T-bet or GATA-3 alone could enhance, and NFATc2 could further synergize with either of them to increase, icos transcription. Although T-bet acted on the icos promoter, GATA-3 operated via an icos 3-untranslated region element. Interestingly, NFATc2 was found to bind promiscuously the icos promoter in developing Th0, Th1, and Th2 cells but became selectively associated with T-bet at the promoter and with GATA-3 at the 3-untranslated region in fully differentiated Th1 and Th2 cells, respectively. Collectively, our results reveal a temporally evolving circuit in which the nonselectively expressed NFATc2 cooperates with Th-restricted T-bet or GATA-3 to direct transcription of a costimulatory gene via distinct regulatory elements in different Th cells undergoing differentiation.

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Section: The Inducible Costimulator (Icos)supporting

confidence: 52%

T Helper Cell-specific Regulation of Inducible Costimulator Expression via Distinct Mechanisms Mediated by T-bet and GATA-3

Tan

Goh

Wong

et al. 2008

Journal of Biological Chemistry

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“…Inducible costimulator (ICOS)-deficient mice are impaired in generating asthmatic and nematode-induced Th2 responses (46,47), but there is some controversy regarding the target of ICOS action. Dong and colleagues (48) reported that ICOS can induce IL-4-independent early IL-4 transcription, also targeting NFATc1.…”

Section: Discussionmentioning

confidence: 99%

Signals from OX40 regulate nuclear factor of activated T cells c1 and T cell helper 2 lineage commitment

Song

Sugie

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

104

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T cell helper type 2 (Th2) differentiation is driven by a source of IL-4 receptor (IL-4R) that mobilizes IL-4R signaling pathways and the transcription factor GATA-3. Naïve CD4 cells can secrete IL-4 independently of IL-4R signals, but how this secretion is regulated is not understood. Here we demonstrate that costimulation through the tumor necrosis factor receptor family molecule OX40, in synergy with CD28, is essential for high levels of nuclear factor of activated T cells c1 to accumulate in the nucleus of a recently activated naïve T cell. This action is not dependent on either IL-4R or IL-2R signals and results in OX40 controlling initial naïve T cell IL-4 transcription. OX40 signals subsequently enhance nuclear GATA-3 accumulation through an IL-4R-dependent action, leading to Th2 differentiation. These data show that, in the absence of an exogenous source of IL-4, OX40 provides a critical synergistic and temporal signal with other noncytokine receptors to modulate nuclear factor of activated T cells c1 and to promote optimal Th2 generation.IL-4 ͉ GATA-3

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“…Expression of ICOSL has been shown to provide costimulation in vitro and enhance T cell-dependent antibody responses and cytokine production from CD4 ϩ T cells in vivo (3,5,17). Moreover, recent results reveal that blockade of ICOS/ICOSL interaction also inhibits T H 1-regulated effector phases in acute allograft rejection and experimental induction of autoimmune encephalomyelitis, leading to increased allograft acceptance and prevention of the disease (18,19). In addition, it appears that ICOS stimulation also has a prominent role in secondary cytotoxic CD8 ϩ T cell responses, leading to effective mobilization of adoptively transferred T cells (20).…”

Section: Successful Antigen-specific T Cell Stimulation Via the T Celmentioning

confidence: 99%

Tumor Necrosis Factor-α Regulates the Expression of Inducible Costimulator Receptor Ligand on CD34+ Progenitor Cells during Differentiation into Antigen Presenting Cells

Richter¹,

Hayden-Ledbetter²,

Irgang³

et al. 2001

Journal of Biological Chemistry

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The inducible costimulator receptor (ICOS) is a third member of the CD28 receptor family that regulates T cell activation and function. ICOS binds to a newly identified ligand on antigen presenting cells different from the CD152 ligands CD80 and CD86. We used soluble ICOSIg and a newly developed murine anti-human ICOS ligand (ICOSL) monoclonal antibody to further characterize the ICOSL during ontogeny of antigen presenting cells. In a previous study, we found that ICOSL is expressed on monocytes, dendritic cells, and B cells. To define when ICOSL is first expressed on myeloid antigen presenting cells, we examined ICOSL expression on CD34 ؉ cells in bone marrow. We found that CD34 bright cells regardless of their myeloid commitment were ICOSL ؊ , whereas ICOSL was first expressed when CD34 expression diminished and the myeloid marker CD33 appeared. However, acute myeloid leukemia cells were ICOSL-negative, whereas among B-cell malignancies only some cases of the most mature tumors such as prolymphocytic leukemia and hairy cell leukemia were positive. Next, we investigated purified CD34؉ hematopoietic progenitor cells that did not constitutively express ICOSL but were induced to express ICOSL within 12 h after granulocyte/macrophage colony-stimulating factor/tumor necrosis factor ␣ (TNF-␣) stimulation. Interestingly, ICOSL was induced prior to CD80/CD86 induction on CD34؉ cells so that ICOSL was expressed in the absence of CD80/CD86. This suggests that ICOSL is an early differentiation marker along the monocytic/ dendritic maturation pathway. Induction of ICOSL was dependent on TNF-␣ and was regulated via NF-B as revealed by use of inhibitors specific for IB␣ phosphorylation such as BAY 11-7082 and BAY 11-7085. The antigen presenting capacity of TNF-␣ stimulated CD34 ؉ cells was strongly inhibited by ICOSIg fusion proteins or by NF-B inhibition. Thus, TNF-␣-induced ICOSL expression seemed to be functionally important for the costimulatory capacity of CD34 ؉ hematopoietic progenitor cells.Successful antigen-specific T cell stimulation via the T cell receptor (TCR) 1 -CD3 complex (TCR⅐CD3) requires costimulatory signals by the CD28 receptor family. During this process, CD28 or CD152 (CTLA-4) expressed on T cells is engaged by the ligands CD80 (B7-1) or CD86 (B7-2) expressed on antigen presenting cells (1, 2). The inducible costimulator (ICOS) is a recently defined third member of the CD28 family, but unlike CD28, it is not constitutively expressed on T cells (3). ICOS expression requires the activation of T cells via the TCR⅐CD3 complex. ICOS shows structural homology to CD28 and CD152, but it differs in the MYPPPY homology domain necessary for binding of CD28/CD152 to CD80 or CD86 (4). Engagement of ICOS, like CD28, can mediate potent costimulation of T cells (3,5), and promotes T cell proliferation at levels similar to those observed after CD28 triggering but without the accompanying increase in IL-2 production. Instead, ICOS up-regulates expression of IL-4, IL-5, GM-CSF, IFN-␥, TNF-␣, and IL-10 (3, 6). Blocking t...

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ICOS is critical for T helper cell–mediated lung mucosal inflammatory responses

Cited by 257 publications

References 52 publications

T Helper Cell-specific Regulation of Inducible Costimulator Expression via Distinct Mechanisms Mediated by T-bet and GATA-3

T Helper Cell-specific Regulation of Inducible Costimulator Expression via Distinct Mechanisms Mediated by T-bet and GATA-3

Signals from OX40 regulate nuclear factor of activated T cells c1 and T cell helper 2 lineage commitment

Tumor Necrosis Factor-α Regulates the Expression of Inducible Costimulator Receptor Ligand on CD34+ Progenitor Cells during Differentiation into Antigen Presenting Cells

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