Human basophils are a source of ‐ and are differentially activated by ‐ IL‐31

Raap, Ulrike; Gehring, Manuela; Kleiner, Svea; Rüdrich, Urda; Eiz‐Vesper, Britta; Haas, Helmut; Kapp, Alexander; Gibbs, Bernhard F.

doi:10.1111/cea.12875

Cited by 104 publications

(109 citation statements)

References 37 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although main source of IL‐31 is Th2 cells, recent studies have suggested that granulocytes are an additional source of IL‐31 . Human β‐defensins and cathelicidin stimulate human mast cells to produce and secrete IL‐31 .…”

Section: The Source Of Il‐31mentioning

confidence: 99%

“…Mast cells from MPD patients exhibit increased IL‐31 secretion under IgE stimulation . Human basophils serve as a source of IL‐31 in the skin of chronic spontaneous urticaria patients …”

Section: The Source Of Il‐31mentioning

confidence: 99%

“…IL‐31RA is expressed by immune cells such as activated macrophages, dendritic cells, eosinophils and basophils, as well as by epidermal keratinocytes and cutaneous peripheral nerves (Figure ) …”

Section: Target Cells and Effects Of Il‐31mentioning

confidence: 99%

See 2 more Smart Citations

Interleukin‐31 and interleukin‐31 receptor: New therapeutic targets for atopic dermatitis

Nakashima

Otsuka

Kabashima

2018

Experimental Dermatology

115

116

View full text Add to dashboard Cite

Atopic dermatitis (AD) is characterized by chronic, eczematous, severe pruritic skin lesions caused by skin barrier dysfunction and T helper (Th)2 cell-mediated immunity.Interleukin (IL)-31 is a potent pruritogenic cytokine primarily produced by Th2 cells. [21] Human basophils serve as a source of IL-31 in the skin of chronic spontaneous urticaria patients.[17] | THE RECEP TOR OF IL-31The receptor for IL-31 consists of a heterodimer of IL-31 receptor α-chain (IL-31RA) and oncostatin M receptor β-chain (OSMR β).Intracellular signalling involving binding of the IL-31 receptor by IL-31 is mediated by the Janus kinase (JAK)-signal transducer and activator of transcription (STAT), phosphatidylinositol-3 kinase (PI3K)/ AKT (also known as protein kinase B or PKB) and mitogen-activated protein kinase (MAPK) pathways (Figure 1). [15,22] Phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) alone is insufficient to activate JAK1/JAK2 and STAT3. [23,24] Furthermore, it has been reported that missense mutations in the OSMR β gene were identified in the patients of familial primary localized cutaneous amyloidosis (FPLCA), hereditary skin disease associated with severe pruritus and deposition of amyloid material in the dermis. [25][26][27] OSMRβ | TARG E T CELL S AND EFFEC TS OF IL-31IL-31RA is expressed by immune cells such as activated macrophages, dendritic cells, eosinophils and basophils, as well as by epidermal keratinocytes and cutaneous peripheral nerves ( Figure 2). [12,17,19,28] | Immune cellsThe levels of IL-31RA expressed on human monocytes and macrophages are significantly elevated by Staphylococcal exotoxins. [29] Human dendritic cells significantly upregulate IL-31RA expression upon stimulation with interferon (IFN)-γ, and IL-31-stimulated dendritic cells release several pro-inflammatory cytokines such as tumor necrosis factor TNF)-α, IL-6, CXCL8, CCL2 CCL5 and CCL22. [30] IL-31RA expression by human mast cells is also upregulated by FcεRI aggregation. [31] Human basophils also express IL-31 receptors.IL-31 was shown to induce the secretion of IL-4 and IL-13 by basophils in vitro and to stimulate basophil chemotaxis.[17] IL-31-stimulated human eosinophils produced pro-inflammatory cytokines (IL-6and IL-1α) and chemokines (eg CXCL1, CCL2 and CCL5). Moreover, these phenomena were significantly upregulated in eosinophils cocultured with fibroblasts or keratinocytes in conjunction with IL-31 stimulation. [19,20] | Epidermal keratinocytesHuman epidermal keratinocytes abundantly express IL-31RA andOSMRβ. Epidermal keratinocytes of AD patients express high levels of IL-31RA compared with those of healthy subjects. IL-31 upregulates the expression levels of various chemokines, such as CCL17/TARC, CCL19/MIP-3β, CCL22/MDC, CCL23/MIP-3, CCL4/ MIP-1β and CXCL1/GRO1α in normal human epidermal keratinocytes (NHEKs). [1] In addition, IL-31 affects keratinocyte differentiation. IL-31 was shown to reduce the expression of epidermal keratinocyte differentiation-associated molecules such as filaggrin, c...

show abstract

Section: The Source Of Il‐31mentioning

confidence: 99%

Section: The Source Of Il‐31mentioning

confidence: 99%

See 1 more Smart Citation

Interleukin‐31 and interleukin‐31 receptor: New therapeutic targets for atopic dermatitis

Nakashima

Otsuka

Kabashima

2018

Experimental Dermatology

115

116

View full text Add to dashboard Cite

show abstract

“…Clinical trials are currently in progress to test the efficacy of a mAb neutralizing IL‐4 and IL‐13 (eg, dupilumab) in severe asthma . Human basophils produce IL‐3 and IL‐31 following IgE‐dependent activation. It has been reported that basophils secrete IL‐25 (IL‐17E) .…”

Section: Mediators Produced By Mast Cells and Basophilsmentioning

confidence: 99%

“…Itch is also stimulated through H4 receptors as well as by the cytokine IL‐31 and it appears likely that combinational therapeutic approaches will in future more completely eliminate symptoms of itch. Interestingly, recent reports show that basophils are an important source of IL‐31 and that IL‐31 levels correlate to the severity of symptoms in atopic dermatitis, further highlighting their role in contributing to this crucial symptom of allergy. While IL‐31 has been shown in mast cells from mastocytosis patients it is currently unknown whether mast cells from healthy or allergic donors express the cytokine.…”

Section: Role Of Mast Cells and Basophils In Health And Diseasementioning

confidence: 99%

Human mast cells and basophils—How are they similar how are they different?

Varricchi

Raap

Rivellese

et al. 2018

Immunological Reviews

127

116

View full text Add to dashboard Cite

Mast cells and basophils are key contributors to allergies and other inflammatory diseases since they are the most prominent source of histamine as well as numerous additional inflammatory mediators which drive inflammatory responses. However, a closer understanding of their precise roles in allergies and other pathological conditions has been marred by the considerable heterogeneity that these cells display, not only between mast cells and basophils themselves but also across different tissue locations and species. While both cell types share the ability to rapidly degranulate and release histamine following high-affinity IgE receptor cross-linking, they differ markedly in their ability to either react to other stimuli, generate inflammatory eicosanoids or release immunomodulating cytokines and chemokines. Furthermore, these cells display considerable pharmacological heterogeneity which has stifled attempts to develop more effective anti-allergic therapies. Mast cell- and basophil-specific transcriptional profiling, at rest and after activation by innate and adaptive stimuli, may help to unravel the degree to which these cells differ and facilitate a clearer understanding of their biological functions and how these could be targeted by new therapies.

show abstract

In chronic spontaneous urticaria, IgE and C‐reactive protein are linked to distinct microRNAs and interleukin‐31

Karstarli Bakay,

Demir,

Cicek

et al. 2023

Clinical & Translational All

View full text Add to dashboard Cite

BackgroundChronic spontaneous urticaria (CSU) is a common and disabling disease. Assessments of IgE and C‐reactive protein (CRP) are recommended in the diagnostic work‐up, but the role and clinical relevance of these biomarkers are not well characterized. Moreover, it remains unknown if elevated levels of IgE or CRP are linked to CSU microRNA (miRNA) signatures or interleukin 31 (IL‐31).MethodsWe measured IgE and CRP serum levels in 47 CSU patients (and 45 healthy controls) and determined CSU disease activity using the urticaria activity score (UAS7). Expression levels of miR‐155 and miR‐221 were assessed by RT‐PCR, and IL‐31 levels were determined by ELISA.ResultsTotal IgE and CRP levels were independently increased in CSU patients. IgE and CRP levels were highest and lowest in patients with high and mild disease activity. IgE levels correlated with miR‐155 levels, whereas CRP levels correlated with miR‐221 levels. miR‐155 and miR‐221 were significantly overexpressed in CSU patients. ROC analyses linked miRNA‐155 and CSU with a sensitivity of 79% and specificity of 87%, and miRNA‐221 and CSU with a sensitivity of 75% and specificity of 91%. High CRP and miR‐221 expression levels were linked to elevated levels of IgG anti‐TPO and IL‐31.ConclusionIgE and CRP are useful biomarkers for disease activity in CSU, with distinct miRNA profiles. High CRP and miR‐221 levels may point to autoimmune CSU and a role for IL‐31.

show abstract

Human basophils are a source of ‐ and are differentially activated by ‐ IL‐31

Cited by 104 publications

References 37 publications

Interleukin‐31 and interleukin‐31 receptor: New therapeutic targets for atopic dermatitis

Interleukin‐31 and interleukin‐31 receptor: New therapeutic targets for atopic dermatitis

Human mast cells and basophils—How are they similar how are they different?

In chronic spontaneous urticaria, IgE and C‐reactive protein are linked to distinct microRNAs and interleukin‐31

Contact Info

Product

Resources

About