Activation markers of human basophils: CD69 expression is strongly and preferentially induced by IL-3

Yoshimura, Chitose; Yamaguchi, Masao; Iikura, Motoyasu; Izumi, Satoshi; Kudo, Kohsuke; Nagase, Hiroyuki; Ishii, Akira; Walls, Andrew F.; Ra, Chisei; Iwata, Tadahisa; Igarashi, Takashi; Yamamoto, Kazuhiko; Hirai, Koichi

doi:10.1067/mai.2002.123532

Cited by 62 publications

(57 citation statements)

References 28 publications

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“…Our findings regarding the ability of IL-3 to transduce independent signaling cascades are consistent with previous observations that IL-3, unlike the other ␤ c -related cytokines, up-regulates human eosinophil CD86 (27) and down-regulates CCR3 (28). In addition, IL-3 is the most efficient cytokine that up-regulates CD69 on the surface of basophils in comparison with IL-5 and GM-CSF (29). In fact, Mire-Sluis et al (30) demonstrated the induction of independent signaling cascades by IL-3-, IL-5-, and GM-CSF-specific ␣-chains.…”

Section: Discussionsupporting

confidence: 92%

CD48 Is an Allergen and IL-3-Induced Activation Molecule on Eosinophils

Munitz

Bachelet

Eliashar

et al. 2006

The Journal of Immunology

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Eosinophils are involved in a variety of allergic, parasitic, malignant, and idiopathic disorders by releasing a variety of factors including specific granule proteins, lipid mediators, and proinflammatory and immunoregulatory cytokines and chemokines. In addition, they interact with various cell types in the inflamed tissue. Yet, the mechanism of eosinophil activation is still poorly understood. Recently, we described the expression and function of the CD2-subfamily of receptors and especially 2B4 on human eosinophils. In this study we focus on CD48, the high-affinity ligand of 2B4. CD48 is a GPI-anchored protein involved in cellular activation, costimulation, and adhesion, but has not been studied on eosinophils. We demonstrate that human eosinophils from atopic asthmatics display enhanced levels of CD48 expression and that IL-3 up-regulates CD48 expression. Furthermore, cross-linking CD48 on human eosinophils triggers release of eosinophil granule proteins. Assessment of CD48 expression in a murine model of experimental asthma revealed that CD48 is induced by allergen challenge and partially regulated by IL-3. Additionally, anti-IL-3 reduces CD48 expression and the degree of airway inflammation. Thus, CD48 is an IL-3-induced activating receptor on eosinophils, likely involved in promoting allergic inflammation.

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Section: Discussionsupporting

confidence: 92%

CD48 Is an Allergen and IL-3-Induced Activation Molecule on Eosinophils

Munitz

Bachelet

Eliashar

et al. 2006

The Journal of Immunology

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“…The most efficient cytokine inducing GzmB together with other phenotypic and functional alterations is IL-3. [30][31][32] An identical concentration range of IL-3 induces GzmB expression and the persistent facilitation of LTC 4 formation. When the effect of different cytokines was compared, we observed an identical order of efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…10,11,[13][14][15]25 Furthermore, IL-3 has the longest duration of action and can also induce phenotypic alterations of mature basophils. 12,15,[30][31][32] From the Institute of Immunology, Inselspital, University of Bern, Switzerland; the Department of Pneumology, University Medical Clinic, Rostock, Germany; and Sanquin Research, Amsterdam, the Netherlands. For personal use only.…”

mentioning

confidence: 99%

Granzyme B, a novel mediator of allergic inflammation: its induction and release in blood basophils and human asthma

Tschopp

Spiegl

Didichenko

et al. 2006

Blood

156

149

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Histamine, leukotriene C4, IL-4, and IL-13 are major mediators of allergy and asthma. They are all formed by basophils and are released in particularly large quantities after stimulation with IL-3. Here we show that supernatants of activated mast cells or IL-3 qualitatively change the makeup of granules of human basophils by inducing de novo synthesis of granzyme B (GzmB), without induction of other granule proteins expressed by cytotoxic lymphocytes (granzyme A, perforin). This bioactivity of IL-3 is not shared by other cytokines known to regulate the function of basophils or lymphocytes. The IL-3 effect is restricted to basophil granulocytes as no constitutive or inducible expression of GzmB is detected in eosinophils or neutrophils. GzmB is induced within 6 to 24 hours, sorted into the granule compartment, and released by exocytosis upon IgE-dependent and -independent activation. In vitro, there is a close parallelism between GzmB, IL-13, and leukotriene C4 production. In vivo, granzyme B, but not the lymphoid granule marker granzyme A, is released 18 hours after allergen challenge of asthmatic patients in strong correlation with interleukin-13. Our study demonstrates an unexpected plasticity of the granule composition of mature basophils and suggests a role of granzyme B as a novel mediator of allergic diseases.

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“…Although several cytokines, such as nerve growth-factor (NGF), IL-5, and granulocyte macrophage colony-stimulating factor (GM-CSF), can transiently prime basophils for enhanced mediator release, [36][37][38] several studies from our and other groups showed that IL-3 is a unique and potent regulator of the phenotype and function of mature basophils. [39][40][41][42][43][44][45][46][47][48] Among a large number of ligands studied, including the priming cytokines and IL-1, IL-3 is the only known cytokine that directly induces secretion of low levels of IL-4 and IL-13, and most efficiently promotes cytokine expression in synergy with C5a or Fc⑀RI-activation. 39,43,44 Here, we investigated receptor expression, the signaling pathways, and biologic effects of IL-33 and IL-18 in blood basophils and also examined which cell types in peripheral blood are the direct targets of IL-33.…”

Section: Introductionmentioning

confidence: 99%

Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33

Pecaric‐Petkovic

Didichenko

Kaempfer

et al. 2009

Blood

385

363

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IntroductionCytokines of the interleukin (IL)-1 family are major proinflammatory and immunoregulatory mediators that act through receptors of the Toll-like/IL-1-receptor (TLR/IL-1R) superfamily. Due to homologous intracellular Toll/interleukin-1 receptor (TIR) domains, IL-1 family members and TLR-ligands activate very similar signaling pathways leading to NF-B-and MAPKactivation. 1 IL-1␣ and IL-1␤, the prototypic family members, are generated in response to exogenous and endogenous danger signals and act as chief inflammatory mediators in many inflammatory conditions. 2 Recent studies indicate that IL-1 may also participate in inflammatory pathologies and auto-immune diseases involving Th17-type T-helper cells. [3][4][5] By contrast, IL-18 is best known for its role in Th1-type immune responses because it strongly amplifies IFN-␥ production in natural killer (NK) cells and Th1 cells in synergy with However, several lines of evidence mainly derived from mouse models indicate that IL-18 can also play a role in allergic diseases and defense against helminths. 6,7 For example, in the absence of IFN-␥ signaling, IL-18 increases immunoglobulin E (IgE) levels and promotes a Th2-type pathology. 8 It has been suggested that this is due to the antigen-independent action of IL-18 on cells of the "innate allergic response," basophils and mast cells. 7 Bone marrow-derived c-Kit Ϫ /Fc⑀RI ϩ mouse "basophil-like" cells express IL-18 receptors (IL-18R), and IL-18 induces IL-4 and IL-13 expression in an antigen-independent manner as efficiently as In the human system, IL-18 primes basophilic KU812 cells for enhanced leukotriene C 4 (LTC 4 ) production. 9 Furthermore, a recent screen of novel CD antigens revealed that blood basophils express IL-18R and IL-18R-accessory protein (IL-18Rap), 10 indicating that IL-18 may also act on human basophils.A soluble form of an IL-1R family member ST2 (sST2; also called T1) has been cloned many years ago. sST2 is formed by many cells and increased sST2 levels are found in inflammatory conditions, including allergic asthma. [11][12][13] The expression of transmembrane ST2-receptor (ST2L), however, is largely restricted to cells of hematopoietic origin. ST2L is expressed by mouse bone marrow-derived mast cells (BMMCs) and is a stable marker of mouse, but not human, Th2-lymphocytes. [14][15][16][17] In the absence of a known ligand, the biologic roles of ST2 have been extensively studied in several mouse models using ST2-antibodies, sST2-constructs, and ST2-KO-mice. 14,18 Although the interpretations were sometimes conflicting, most studies indicate an important contribution of ST2 in Th2-type immune responses and allergic inflammation. The biology of ST2 is further complicated by a possible direct antiinflammatory action of sST2, and by the fact that the TIR domain of ST2L appears to be a negative regulator of 20 Research on ST2 strongly gained momentum by the recent discovery of its ligand, the novel IL-1 family member IL-33. 21 Like IL-1␣, the human IL-33 precursor (proIL-33) is a nuclear pr...

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Activation markers of human basophils: CD69 expression is strongly and preferentially induced by IL-3

Cited by 62 publications

References 28 publications

CD48 Is an Allergen and IL-3-Induced Activation Molecule on Eosinophils

CD48 Is an Allergen and IL-3-Induced Activation Molecule on Eosinophils

Granzyme B, a novel mediator of allergic inflammation: its induction and release in blood basophils and human asthma

Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33

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