A critical role for NF-κB in Gata3 expression and TH2 differentiation in allergic airway inflammation

Das, Jyoti; Chen, Chang-Hung; Yang, Liyan; Cohn, Lauren; Ray, Prabir; Ray, Anuradha

doi:10.1038/83158

Cited by 484 publications

(430 citation statements)

References 39 publications

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“…Interestingly, mice lacking p50 are unable to mount an asthma-like airway T H 2 response, and do not induce GATA-3 expression during T-cell stimulation under T H 2 differentiating conditions (Das et al, 2001). Consistent with this finding, BCL-3-deficient T cells also fail to undergo T H 2 differentiation.…”

Section: T-cell Responses Mediated By Nf-kbmentioning

confidence: 58%

NF-κB and the immune response

2006

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Section: T-cell Responses Mediated By Nf-kbmentioning

confidence: 58%

NF-κB and the immune response

2006

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“…Although IL-13 is mainly produced by T cells [39,40], several sources of IL-13 have been suggested, including human and mouse NK cells [16,17], NKT cells [41], basophils [25,26] and mast cells [42]. To specifically address the question of which cell populations produce IL-13 during this IL-4/B7-independent in vivo immune response to T. muris, we performed cell sorting and quantitative RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous findings support this concept and further suggest that IL-13 can mediate resistance to T. muris in the absence of both IL-4 signaling and B7 costimulation [8]. These studies indicated either a novel B7-independent pathway of CD4 + T cell differentiation leading to IL-13 but not IL-4 expression or an alternative cell source that can differentiate to produce IL-13 if B7 is blocked and/or IL-4 is neutralized.Although IL-13 is mainly produced by T cells [39,40], several sources of IL-13 have been suggested, including human and mouse NK cells [16,17], NKT cells [41], basophils [25,26] and mast cells [42]. To specifically address the question of which cell populations produce IL-13 during this IL-4/B7-independent in vivo immune response to T. muris, we performed cell sorting and quantitative RT-PCR.…”

mentioning

confidence: 99%

IL‐18 stimulates IL‐13‐mediated IFN‐γ‐sensitive host resistance in vivo

Liu

Whitmire

et al. 2006

Eur J Immunol

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IL-4 and IL-13 are up-regulated during in vivo responses to many nematode parasites, but increasing evidence suggests that increases in IL-13 can also occur independently of the IL-4-dominant Th2 response. Blocking B7 after Trichuris muris inoculation inhibits resistance and IL-4 elevations, instead resulting in an IFN-c-dominant response associated with susceptibility. However, blocking IFN-c under these conditions restores IL-13-dependent resistance. In this study, we examined the mechanism of IL-13 upregulation and associated protection during this in vivo immune response. CD4 + T cells and DX5 + TCR -cells were identified as the major producers of IL-13, and the DX5 + TCRcells were phenotyped as NK cells, since they expressed CD11b, IL-2Rb and Ly49C but not c-kit or FceRI. NK cell-derived IL-13 elevations were T cell-dependent, as CD4 + T cell depletion blocked IL-13 production by mesenteric lymph node cells and induced susceptibility. IL-13 expression was increased independently of IL-12; however, blocking IL-18 function inhibited IL-13 production and increased susceptibility. These results indicate that CD4 + T cells and NK cells are the major sources of IL-13 during the in vivo Th1 response induced by B7 blockade and that under these conditions, IL-18 is specifically required for the in vivo up-regulation of IL-13 production and associated host protection. IntroductionThe host protective response that develops following infection varies greatly with the particular pathogen. The type 2 immune response, associated with high levels of IL-4, IL-13 and other Th2 cytokines, provides protection against intestinal nematode parasites [1-3], while type 1 immunity, associated with an IFNc-dominant response, mediates resistance against many viruses and bacteria [4,5]. The events that lead to the development of type 1 and type 2 immunity are generally thought to be distinct, and as each response matures, production of characteristic cytokines can down-regulate the reciprocal response, resulting in further polarization.Typically, type 2 responses leading to resistance require the development of IL-4-producing effector CD4 + T cells, which then utilize autocrine IL-4 for their rapid expansion [3]. These Th2 cells mediate worm expulsion through their production of Th2 cytokines, with IL-4 and IL-13 being particularly important for the expulsion of gastrointestinal nematode parasites [1,2]. The development and expansion of IL-4-producing T cells is preferentially dependent on B7 costimulatory molecules [6,7], and in a number of infectious diseases, B7 blockade can actually deviate a Th2 response to an IFN-c-dominant Th1 response [8,9]. In the Th2 cell differentiation model just described, blockade of IL-4 production with B7 antagonists would be expected to also inhibit IL-13 production. However, other studies suggest that under certain circumstances IL-4 and IL-13 are regulated independently, and certain signaling pathways involving c-maf [10] and can differentially regulate these two cytokines. Consistent with these fin...

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“…The binding of IL-1a and IL1b to the IL-1 type 1 receptor [27] triggers a signaling cascade that results in the activation of NF-jB and AP1. NF-jB-deficient T cells show impaired ability to polarize to Th2-type cells [28] and express GATA-3, a transcription factor known to control Th2 differentiation [29]. Thus, NFjB family members play a critical role in Th2 development.…”

Section: Discussionmentioning

confidence: 99%

Interleukin 1 plays a major role in the development of Th2‐mediated immunity

Helmby

Grencis

2004

Eur J Immunol

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Expulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper (Th)2-type response, involving interleukin (IL)-4, IL-9 and IL-13. Here, we show that Th2 responseassociated resistance is dependent on the presence of IL-1a and IL-1b. When lymph node cells from naive IL-1a-or IL-1b-deficient mice were subjected to Th2 polarization in vitro, they failed to polarize in the presence of IL-4 alone, but required the addition of exogenous IL-1a or IL-1b. Furthermore, we demonstrate that both IL-1a-and IL-1b-deficient mice are susceptible to chronic T. muris infection and that the inability to expel the worms is associated with a defect in the development of a Th2 response in the mesenteric lymph nodes. These results provide the first demonstration of the critical role of IL-1 in regulating Th2 responses during gastrointestinal nematode infection.

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A critical role for NF-κB in Gata3 expression and TH2 differentiation in allergic airway inflammation

Cited by 484 publications

References 39 publications

NF-κB and the immune response

NF-κB and the immune response

IL‐18 stimulates IL‐13‐mediated IFN‐γ‐sensitive host resistance in vivo

Interleukin 1 plays a major role in the development of Th2‐mediated immunity

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