Indeed, basophils from ILdeficient mice could not induce the development of T h 2 cells under neutral conditions Similar to our results, Sokol et al.
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To provide definitive proof that basophils can function as APCs, it was necessary to demonstrate the ability of basophils to take up and process whole-OVA protein into OVA peptide fragments. Basophils have a unique potential to increase their capacity to induce IL-4 when they are cross-linked with antigen plus antigen-specific IgE 16— It is thus crucial to demonstrate the potential of basophils to increase APC activity when pulsed with antigen—IgE complexes. In the absence of DCs, basophils are able to generate T h 2-cell responses in vivo in response to complexes of antigen plus antigen-specific IgE, in response to the protease allergen papain or in response to helminthic parasites 28— Only OVA-pulsed basophils promptly and strongly induced T h 2 cells in the spleen.
Yoshimoto, unpublished data. In a complementary study, Sokol et al. The transfer of antigen-loaded basophils into wild-type or MHC class II-deficient mice induced T h 2-cell differentiation in vivo.
Immunological Mechanisms in Allergic Diseases and Allergen Tolerance: The Role of Treg Cells
These two independent basophil-adoptive transfer studies 28 , 29 confirmed that MHC class II-positive basophils are sufficient for the initiation of T h 2 responses in vivo. Depletion of basophils significantly diminished these T h 2 responses. Role of basophils in amplification of the T h 2—IgE response. B Anti-IgE therapy omalizumab may interfere with the generation of allergen-pulsed basophils and therefore inhibit endogenous basophil-dependent amplification of T h 2 responses in vivo.
Three independent groups have clearly demonstrated that basophils have the antigen-presenting capacity to promote T h 2 immunity both in vitro and in vivo 28— As mentioned above, however, DCs have been clearly shown to induce T h 2-cell differentiation in vitro and in vivo via notch ligands and OX40L 11 , In addition, a potential role for alternative activated macrophages M2a in T h 2 induction has been noted Recently, Kim et al. Similar to papain immunization 29 , circulating basophils were transiently recruited into draining lymph nodes following N.
Similarly, we demonstrated that N. Taken together, these data suggest that there are multiple pathways leading to T h 2-cell differentiation in vivo. Atopic individuals are characterized by having more basophils at the sites of allergic inflammation 19— Once such individuals begin to produce antigen-specific IgE, the amount of complexes of antigen plus antigen-specific IgE can steadily increase, allowing basophils to augment their uptake of IgE complexes.
It is thus possible that mature basophils at allergic inflammation sites, characterized by abundant production of IL-3 and other factors, do express HLA-DR. This would mean that basophils could become potent APCs and induce progressive allergic inflammation in these individuals. Furthermore, immune complexes of allergen and the resultant allergen-specific IgE preferentially augment the development of allergen-specific T h 2 responses in an endogenous basophil-dependent manner.
It has been reported that anti-IgE therapy omalizumab is effective for T h 2—IgE-mediated diseases such as bronchial asthma The rationale for such therapy is that anti-IgE antibodies are believed to interfere with IgE-mediated activation of mast cells and basophils. On the basis of our results, there is another rationale for such therapy; namely, inhibition of the generation of allergen-pulsed basophils Fig. Basophils might thus represent an important therapeutic target cell. Oxford University Press is a department of the University of Oxford.
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Article Contents. Basophils as a source of early IL-4 for T h 2 differentiation. Basophils as APCs in vitro. Basophils as APCs in vivo. Controversies in this field. Concluding remarks. Editor's Choice. Basophils as T h 2-inducing antigen-presenting cells Tomohiro Yoshimoto. Oxford Academic. Google Scholar. Article history. Cite Citation. Permissions Icon Permissions. View large Download slide. Two types of murine helper T cell clone. However, further investigations are needed to determine which chemokine receptors are involved in mediating basophil infiltration of skin lesions and what specific circumstances elicit this infiltration.
Systemic lupus erythematosus SLE is a chronic inflammatory disease involving multiple organs, including skin, brain, lungs, and kidneys [ 8 , 9 ].
Skin lesions are a common presentation in patients with SLE. Skin involvement is second only to joint manifestations as the predominant manifestation of SLE, both at onset and later stages of the disease [ 12 , 13 ]. Cutaneous manifestations are correlated with disease activity in SLE, which gives them diagnostic value [ 14 ]. As was known, several types of immune cells [ 15 - 17 ], including basophils [ 18 ] have been reported to exacerbate SLE by amplifying production of autoantibodies and inflammatory cytokines.
However, we do not know if basophils infiltrate skin lesions in SLE, and if they do, what are the mechanisms of this infiltration. This study aimed to investigate basophil infiltration into SLE skin lesions and the infiltration mechanism, both in patients with SLE and in vitro , which should provide novel insights into the pathogenesis of skin lesions in SLE. Twenty healthy control subjects Table 1 with no age, sex, or race differences were also enrolled. All subjects provided peripheral blood samples. Nine of the SLE patients with cutaneous lesions underwent skin biopsies to detect tissue basophils Table 2.
Normal skin tissue from cases of trauma or surgery were used as compared controls. All participants provided written informed consent. Demographic characteristics of patients with active cutaneous lupus lesions. DMEM alone served as the spontaneous-migration control, and cells pipetted into the lower well served as a positive control.
Following the incubation period, migrated cells were harvested and stained for flow cytometric analysis as described in Materials and Methods 2. All statistical analyses were performed using SPSS Two-group comparisons were performed using an independent one-sample t-test. Compared with healthy controls, the basophils in peripheral blood of SLE patients were activated and had increased expression of the activation marker CDc Fig. However, the number Fig. These results indicate that peripheral basophil activation could play a role in SLE.
Activation and numbers of peripheral basophils in SLE patients. To further explore the decreased numbers of peripheral basophils in SLE patients, we examined the recruitment of basophils to skin lesions in SLE patients [ 5 ]. In eight of nine SLE patients with cutaneous lesions receiving skin biopsy, basophils were located in the superficial dermis and perivascular regions of inflammatory sites Fig.
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Basophils were not present in normal skin tissue Fig. Infiltration of basophils in skin lesions of SLE patients. Basophils were stained using 2D7 antibody. Black rectangles indicate the areas of the field shown in higher magnification at the corners of the panel. Chemokines and their receptors are involved in the regulation of infiltration into cellular inflammatory sites.
Therefore, we investigated the mechanisms mediating basophil infiltration in skin lesions of SLE patients by evaluating the levels of these CCRs in peripheral basophils. Peripheral basophils from SLE patients had a higher migration rate than those from healthy controls Fig. Basophils orchestrate chronic allergic dermatitis and protective immunity against helminths. Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks.
Barton , Andrew G. Farr , Ruslan Medzhitov. Basophils are essential initiators of a novel type of chronic allergic inflammation. Close Share. Figure 1 Mouse models of basophil deficiency. In Mcpt8DTR mice, the diphtheria toxin receptor is genetically engineered to be expressed only on basophils. Therefore, DT injection induces selective depletion of basophils.