T follicular regulatory cells and IL-10 promote food antigen–specific IgE

Xie, Markus M.; Chen, Qiang; Liu, Hong; Yang, Kai; Koh, Byunghee; Wu, Hao; Maleki, Soheila J.; Hurlburt, Barry K.; Cook‐Mills, Joan M.; Kaplan, Mark H.; Dent, Alexander L.

doi:10.1172/jci132249

Cited by 60 publications

(58 citation statements)

References 71 publications

(114 reference statements)

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“…In contrast to T FR cells in allergic asthma and rhinitis as described above, Xie et al 85 recently reported a surprising result in that the loss of T FR cells reduced peanut‐specific IgE titers but increased nonspecific IgE levels in a peanut‐induced food allergy model. They further revealed that the promotion of antigen‐specific IgE production by T FR cells is dependent on IL‐10 85 . However, this conflicted with the reported suppressive role of IL‐10 in IgE production, 127 thereby warranting further investigation.…”

Section: Tfh and Tfr Cells In Allergic Diseasesmentioning

confidence: 94%

“…Intriguingly, food allergens induced the generation of T FH 2 cells in gut‐associated lymphoid tissues and drove the spontaneous IgE elevation, even in mice without commensal microbiota (germ‐free housing) 126 . In contrast to T FR cells in allergic asthma and rhinitis as described above, Xie et al 85 recently reported a surprising result in that the loss of T FR cells reduced peanut‐specific IgE titers but increased nonspecific IgE levels in a peanut‐induced food allergy model. They further revealed that the promotion of antigen‐specific IgE production by T FR cells is dependent on IL‐10 85 .…”

Section: Tfh and Tfr Cells In Allergic Diseasesmentioning

confidence: 97%

“…Consistently, patients with CTLA‐4 haploinsufficiency displayed higher frequencies of cT FH cells with concomitantly lower frequencies of cT FR cells than healthy subjects 83 . Although several studies have shown that T FR cell‐derived IL‐10 promoted GC responses and IgE production in mice, 84,85 IL‐10‐producing follicular T cells appear to inhibit IgE production in humans 86,87 . Despite these progresses, the molecular mechanisms underlying the suppressive function of T FR cells requires further investigation, particularly in comparison to conventional T REG cells.…”

Section: Development Phenotype and Role Of Tfr Cellsmentioning

confidence: 99%

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Roles of follicular helper and regulatory T cells in allergic diseases and allergen immunotherapy

Yao

Chen

et al. 2020

Allergy

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Allergic diseases are characterized by overactive type 2 immune responses to allergens and immunoglobulin E (IgE)‐mediated hypersensitivity. Emerging evidence suggests that follicular helper T (TFH) cells, rather than type 2 T‐helper (TH2) cells, play a crucial role in controlling IgE production. However, follicular regulatory T (TFR) cells, a specialized subset of regulatory T (TREG) cells resident in B‐cell follicles, restricts TFH cell‐mediated help in extrafollicular antibody production, germinal center (GC) formation, immunoglobulin affinity maturation, and long‐lived, high‐affinity plasma and memory B‐cell differentiation. In mouse models of allergic asthma and food allergy, CXCR5+ TFH cells, not CXCR5− conventional TH2 cells, are needed to support IgE production, otherwise exacerbated by CXCR5+ TFR cell deletion. Upregulation of TFH cell activities, including a skewing toward type 2 TFH (TFH2) and IL‐13 producing TFH (TFH13) phenotypes, and defects in TFR cells have been identified in patients with allergic diseases. Allergen immunotherapy (AIT) reinstates the balance between TFH and TFR cells in patients with allergic diseases, resulting in clinical benefits. Collectively, further understanding of TFH and TFR cells and their role in the immunopathogenesis of allergic diseases creates opportunities to develop novel therapeutic approaches.

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Section: Tfh and Tfr Cells In Allergic Diseasesmentioning

confidence: 94%

Section: Tfh and Tfr Cells In Allergic Diseasesmentioning

confidence: 97%

Section: Development Phenotype and Role Of Tfr Cellsmentioning

confidence: 99%

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Roles of follicular helper and regulatory T cells in allergic diseases and allergen immunotherapy

Yao

Chen

et al. 2020

Allergy

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“…Tfr cells also regulate the immune response to allergens as shown in a mouse model of house dust mite allergy where Tfr cells modulated the activity of Tfh cells [38]. In addition, Tfr cells can directly inhibit B cells via IL‐10 signaling in a model of food allergy [40].…”

Section: Introductionmentioning

confidence: 99%

“…A high BCR affinity would further improve this interaction thus favoring high affinity B cells to develop into PCs that leave the GC. Tfr cells on the other hand prevent the generation and GC exit of PCs that produce unspecific or autoreactive antibodies [38, 40, 62].…”

Section: Introductionmentioning

confidence: 99%

Regulation of the humoral type 2 immune response against allergens and helminths

Haase

Voehringer

2020

Eur J Immunol

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The type 2 immune response is associated with helminth infections and allergic inflammation where antibody production of the IgG1 and IgE isotypes can elicit protective or proinflammatory functions. Studies over the past few years revealed important new insights regarding the regulatory mechanisms orchestrating the humoral type 2 immune response. This includes investigations on B‐cell extrinsic signals, such IL‐4 and IL‐21, derived from different T‐helper cell subsets or discovery of new follicular helper T cells with regulatory or IgE‐promoting activities. In addition, studies on B‐cell intrinsic factors required for germinal center formation and class switch recombination, including the transcription factors STAT3, STAT6, and BCL‐6, led to a better understanding of these processes in type 2 immune responses. Here, we review the current understanding of mechanisms controlling humoral type 2 immunity in vivo including the generation of IgE‐producing plasma cells and the memory IgE response.

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Increase in the prevalence of follicular regulatory T cells correlates with clinical efficacy of sublingual immunotherapy with house dust mites

Murao

Kouzaki

Arai

et al. 2023

Int Forum Allergy Rhinol

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BackgroundAllergic rhinitis (AR) impairs quality of life and affects nearly 40% of the Japanese population. Sublingual immunotherapy (SLIT) is the disease‐modifying treatment for AR, but requires the selection of a biomarker associate with clinical efficacy in patients with AR who are treated with SLIT. The present study sought to examine objective biomarkers used for assessing the clinical efficacy of SLIT.MethodsThe authors examined the effects of 1 year of SLIT treatment with house dust mites (HDMs) using peripheral blood mononuclear cells (PBMCs) and serum from patients with AR. The prevalences of follicular regulatory T (Tfr), type 2 follicular helper T (Tfh2), type 2 helper T (Th2), conventional regulatory T (Treg), and type 1 regulatory T (Tr1) cells were examined by flow cytometry. Serum concentrations of HDM‐specific IgA, IgE, and IgG4 antibodies, and HDM‐induced production of interleukin (IL) 5 and IL‐10 from cultured PBMCs were evaluated by enzyme‐linked immunosorbent assay.ResultsFollowing 1 year of SLIT, the prevalences of Tfr, conventional Treg, and Tr1 cells were significantly increased, whereas that of Th2 cells and Tfh2 cells were significantly decreased; the serum concentration of HDM‐specific IgG4 was significantly increased; and HDM‐induced production of IL‐5 from PBMCs was significantly decreased, while that of IL‐10 was significantly increased. The increase in the prevalence of Tfr cells after SLIT correlated positively with the improvement of clinical symptom scores.ConclusionAn increase in Tfr cells may play an important role in SLIT, and may be a useful indicator for the clinical efficacy of SLIT.

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T follicular regulatory cells and IL-10 promote food antigen–specific IgE

Cited by 60 publications

References 71 publications

Roles of follicular helper and regulatory T cells in allergic diseases and allergen immunotherapy

Roles of follicular helper and regulatory T cells in allergic diseases and allergen immunotherapy

Regulation of the humoral type 2 immune response against allergens and helminths

Increase in the prevalence of follicular regulatory T cells correlates with clinical efficacy of sublingual immunotherapy with house dust mites

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