Basophils Produce IL-4 and Accumulate in Tissues after Infection with a Th2-inducing Parasite

Min, Booki; Prout, Melanie; Hu‐Li, Jane; Zhu, Jinfang; Janković, Dragana; Morgan, Ellen S.; Urban, Joseph F.; Dvorak, Ann M.; Finkelman, Fred D.; Gros, Graham Le; Paul, William E.

doi:10.1084/jem.20040590

Cited by 380 publications

(388 citation statements)

References 51 publications

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“…These studies thus demonstrate differential regulation of IL-4 and IL-13 in T cells by costimulatory molecules during the in vivo immune response, consistent with previous studies indicating that these Th2 cytokines can be differentially regulated by certain transcription factors [10,11]. Our studies further indicate that DX5 + cells are also a major source of IL-13.DX5 has been shown to be expressed by a number of cell types, including NK cells, NK T cells, basophils and some T cells [23,24]. Mast cells and basophils can be distinguished by the expression of the high-affinity IgE receptor (FceRI), which is absent from murine NK cells, and anti-c-kit mAb specifically identifies mast cells [44,45].…”

supporting

confidence: 92%

“…2c). Although DX5 is expressed on the majority of NK cells and NK T cells, it also can be expressed on basophils [23,24]. In addition, both basophils and mast cells have been reported to be associated with protective Th2 responses [25] and to produce IL-4 and IL-13 when stimulated by FceRI or with ionomycin [25,26], suggesting these two cell populations may also be candidate cell types for these DX5 + TCR -IL-13-expressing cells.…”

Section: Resultsmentioning

confidence: 99%

“…DX5 has been shown to be expressed by a number of cell types, including NK cells, NK T cells, basophils and some T cells [23,24]. Mast cells and basophils can be distinguished by the expression of the high-affinity IgE receptor (FceRI), which is absent from murine NK cells, and anti-c-kit mAb specifically identifies mast cells [44,45].…”

Section: Discussionmentioning

confidence: 99%

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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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supporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

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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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“…Recently, mast cells and basophils have been recognized to be able to produce T H 2 cytokines that might be important for T H 2 cell differentiation and T H 2 effector functions. [29][30][31] Given the fact that SHIP-1 has a regulatory role in mast cells, it is reasonable to speculate that SHIP-1 acts as a negative regulator to keep mast cells or basophils in check. When lacking SHIP-1, mast cells and basophils might have increased sensitivity or a decreased threshold for releasing mediators and cytokines, such as IL-4 and IL-13, which might be responsible for the T H 2 phenotype in SHIP-1 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

Src homology 2 domain–containing inositol 5-phosphatase 1 deficiency leads to a spontaneous allergic inflammation in the murine lung

Zheng

Bailey

et al. 2007

Journal of Allergy and Clinical Immunology

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Background-Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP-1) controls the intracellular level of the phosphoinositide 3-kinase product phosphotidylinositol-3,4,5-trisphosphate and functions as a negative regulator of cytokine and immune receptor signaling. Emerging evidence suggests that the phosphoinositide 3-kinase pathway might be involved in allergic inflammation in the lung. However, the functional relevance of SHIP-1 in the T H 2 activation pathway has not been established. SHIP-1 −/− mice have spontaneous myeloproliferative inflammation in the lung, the nature of which has not been elucidated. We hypothesized that SHIP-1 plays an important role as a regulator in pulmonary allergic inflammation and in maintaining lung homeostasis.

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“…76 Leukotriene D4 did not induce IL-13 or IL-5 expression that as mentioned is mainly promoted by IL-25 and IL-33, illustrating a compartmentalized activation mechanism. IL-4 is also produced by basophils 68,77,78 that also is more likely to be important for humoral immunity and thus play a role during challenge infections.…”

Section: Transmissionmentioning

confidence: 99%