Basophils are required for the induction of Th2 immunity to haptens and peptide antigens

Otsuka, Atsushi; Nakajima, Saeko; Kubo, Masato; Egawa, Gyohei; Honda, Tetsuya; Kitoh, Akihiko; Nomura, Takashi; Hanakawa, Sho; Moniaga, Catharina Sagita; Kim, Bongju; Matsuoka, Satoshi; Watanabe, Takeshi; Kabashima, Kenji

doi:10.1038/ncomms2740

Cited by 104 publications

(155 citation statements)

References 31 publications

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“…It was shown that the transcription factors GLI1 and GLI2 activated the SOCS1 promoter, and STAT1 phosphorylation was reduced in cells with active Hh/GLI signaling (28). mRNA levels including IFNg depend on when the samples are collected (29,30). A previous report showed that IFNg mRNA expression in the skin-infiltrated IFNg-producing T cells increased at the peak of 12 hours and diminished after 24 hours in skin allergic inflammation (30).…”

Section: Discussionmentioning

confidence: 99%

Hedgehog Pathway Inhibitors Promote Adaptive Immune Responses in Basal Cell Carcinoma

Otsuka

Dreier

Cheng

et al. 2015

Clinical Cancer Research

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Purpose: Basal cell carcinomas (BCCs) are tumors ignored by immune surveillance. Activated Hedgehog (Hh) signaling within primary cilia is a key driver in the pathogenesis of BCCs. We examined immune alterations during treatment with systemic Hh inhibitors.Experimental Design: We investigated biopsies from patients with BCC before (23 patients) and after 4 weeks of treatment (5 patients) with Hh signaling inhibitor. Ber-Ep4, BCL-2, Ki-67, CD4, CD8, MHC class I, HLA-DR-class II, and SOX9 were analyzed by immunohistochemistry. Primary cilia were analyzed by double immunofluorescence of acetylated tubulin and SOX9. Differential gene expression for 84 cytokines and chemokines was analyzed in 3 patients.Results: After 4 weeks of treatment, we found reduction of Ki-67, SOX9, Ber-EP4, and BCL-2 expression in tumors associated with morphologic signs of squamous differentiation. In addition, the number of cilia-positive BCC cells was significantly decreased. An upregulation of MHC I expression on the cell membranes of residual tumor cells and an influx of CD4 þ , HLA-DR-class II þ, and CD8 þ cells with invasion into the tumor cell nests were found. Finally, qPCR arrays showed the differential expression of genes involved in modulating immune responses. Conclusions:We show that Hh pathway inhibitor-induced tumor regression is accompanied by a dynamic change of the microenvironment with a disruption of immune privilege involving an influx of cytotoxic T cells, activation of the adaptive immune functions, and a profound alteration of the local chemokine/cytokine network.

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Section: Discussionmentioning

confidence: 99%

Hedgehog Pathway Inhibitors Promote Adaptive Immune Responses in Basal Cell Carcinoma

Otsuka

Dreier

Cheng

et al. 2015

Clinical Cancer Research

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“…Basophils alone were reported to polarize T cells towards Th2 for haptens and peptides antigens but needed the presence of DCs for protein antigens [18,19].…”

Section: Basophils and Th2 Cell Responsesmentioning

confidence: 99%

The role of eosinophils and basophils in allergic diseases considering genetic findings

Nadif

Zerimech²,

Matran³

2013

Current Opinion in Allergy &Amp; Clinical Immunology

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2 Purpose of reviewBasophils and eosinophils respectively represent less than 1 and 5% of white blood cells respectively. Their role in asthma and allergic inflammation remains incompletely defined.The present review addresses recent advances regarding the role of these two cell populations in allergic inflammation and asthma regarding both biological and genetic point of view. Recent findingsRegarding eosinophils, the role of interleukin ( SummaryRecent findings from biological and genetic studies on eosinophils and basophils highlight the role of epithelial cell-derived cytokines such as TSLP and IL-33 in asthma and allergic diseases.

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“…Of note, basophils reportedly express H-2M and invariant chain, which are key regulators of peptide loading on MHC-II, at very low levels compared with DCs, raising concerns about the basophil's antigen-processing and presentation ability (21). Moreover, the level of MHC-II expression on basophils varies, depending on experimental conditions, but it is generally much lower than that on professional APCs such as DCs and B cells (5)(6)(7)(8). Thus, the significance of MHC-II expression on basophils and the antigen-presentation capacity of basophils remain controversial (24).…”

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confidence: 99%

“…However, recent studies have revealed that basophils and mast cells play distinct roles in immune responses such as allergic inflammation and protective immunity to parasitic infections (2)(3)(4). Basophils also contribute to immune regulation through their interaction with other types of cells, including T cells (5)(6)(7)(8), monocytes (9,10), innate lymphoid cells (11), fibroblasts (12,13), and endothelial cells (14).…”

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confidence: 99%

Trogocytosis of peptide–MHC class II complexes from dendritic cells confers antigen-presenting ability on basophils

Miyake

Shiozawa

Nagao

et al. 2017

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

106

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Th2 immunity plays important roles in both protective and allergic responses. Nevertheless, the nature of antigen-presenting cells responsible for Th2 cell differentiation remains ill-defined compared with the nature of the cells responsible for Th1 and Th17 cell differentiation. Basophils have attracted attention as a producer of Th2-inducing cytokine IL-4, whereas their MHC class II (MHC-II) expression and function as antigen-presenting cells are matters of considerable controversy. Here we revisited the MHC-II expression on basophils and explored its functional relevance in Th2 cell differentiation. Basophils generated in vitro from bone marrow cells in culture with IL-3 plus GM-CSF displayed MHC-II on the cell surface, whereas those generated in culture with IL-3 alone did not. Of note, these MHC-II–expressing basophils showed little or no transcription of the corresponding MHC-II gene. The GM-CSF addition to culture expanded dendritic cells (DCs) other than basophils. Coculture of basophils and DCs revealed that basophils acquired peptide–MHC-II complexes from DCs via cell contact-dependent trogocytosis. The acquired complexes, together with CD86, enabled basophils to stimulate peptide-specific T cells, leading to their proliferation and IL-4 production, indicating that basophils can function as antigen-presenting cells for Th2 cell differentiation. Transfer of MHC-II from DCs to basophils was also detected in draining lymph nodes of mice with atopic dermatitis-like skin inflammation. Thus, the present study defined the mechanism by which basophils display MHC-II on the cell surface and appears to reconcile some discrepancies observed in previous studies.

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Basophils are required for the induction of Th2 immunity to haptens and peptide antigens

Cited by 104 publications

References 31 publications

Hedgehog Pathway Inhibitors Promote Adaptive Immune Responses in Basal Cell Carcinoma

Hedgehog Pathway Inhibitors Promote Adaptive Immune Responses in Basal Cell Carcinoma

The role of eosinophils and basophils in allergic diseases considering genetic findings

Trogocytosis of peptide–MHC class II complexes from dendritic cells confers antigen-presenting ability on basophils

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