Human basophil chemotaxis and activation are regulated via the histamine H4 receptor

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.

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“…H4R expression has been shown on human mast cells and basophils . H4R activation can modulate the function of mast cells and basophils …”

Section: Inhibitory Receptors On Human Mast Cells and Basophilsmentioning

confidence: 99%

“…164,165 H4R activation can modulate the function of mast cells and basophils. [165][166][167][168][169]…”

Section: Histamine Receptorsmentioning

confidence: 99%

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

Varricchi

Raap

Rivellese

et al. 2018

Immunological Reviews

129

116

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“…Histamine and HH4R agonist (ST1006) initiate active migration of basophils. A reduction in FcɛRI crosslinking-mediated surface expression of CD63 and CD203c is observed on basophils after pre-incubation with histamine or the HH4R agonist (ST1006) [36] .…”

Section: Basophilsmentioning

confidence: 98%

Histamine H4 Receptor in Allergic Dermatitis

Seike

2017

Journal of Dermatological Research

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Allergic dermatitis, the common skin disease, includes chronic allergic contact dermatitis (CACD) and atopic dermatitis (AD), the Th2 dominant diseases. Histamine aggravates CACD in mice. Histamine H4 receptor (HH4R) is expressed on eosinophils, mast cells, T cells, natural killer cells, antigen presenting cells, basophils, keratinocytes and sensory neurons and is suggested to be related to allergic dermatitis. Administration of the HH4R antagonist JNJ7777120 is effective to the murine CACD models. Furthermore, combination of JNJ7777120 and the histamine H1 receptor antagonist olopatadine hydrochloride is a potent therapeutic target in chronic inflammatory skin diseases such as CACD and AD, since combined therapy is more effective than monotherapy.

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“…These observations suggest that IgE‐mediated basophil migration could be induced without activation and degranulation of basophils in circulation. In case of degranulation and histamine release, binding of histamine to H4 receptors further enhances migration . Repeated exposure over long periods to subthreshold allergen concentrations may also result in basophil desensitization (anergy) .…”

Section: Basophil Migrationmentioning

confidence: 99%

“…In case of degranulation and histamine release, binding of histamine to H4 receptors further enhances migration. 90 Repeated exposure over long periods to subthreshold allergen concentrations may also result in basophil desensitization (anergy). 91,92 The effects of this phenomenon are not yet clear regarding basophil migration.…”

Section: Ige Stimulation For Basophil Migrationmentioning

confidence: 99%

Important and specific role for basophils in acute allergic reactions

Korošec

Gibbs

Rijavec

et al. 2018

Clin Experimental Allergy

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SummaryIgE‐mediated allergic reactions involve the activation of effector cells, predominantly through the high‐affinity IgE receptor (FcεRI) on mast cells and basophils. Although the mast cell is considered the major effector cell during acute allergic reactions, more recent studies indicate a potentially important and specific role for basophils and their migration which occurs rapidly upon allergen challenge in humans undergoing anaphylaxis. We review the evidence for a role of basophils in contributing to clinical symptoms of anaphylaxis and discuss the possibility that basophil trafficking during anaphylaxis might be a pathogenic (to target organs) or protective (preventing degranulation in circulation) response. Finally, we examine the potential role of basophils in asthma exacerbations. Understanding the factors that regulate basophil trafficking and activation might lead to new diagnostic and therapeutic strategies in anaphylaxis and asthma.

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Human basophil chemotaxis and activation are regulated via the histamine H4 receptor

Abstract: These data imply that the H4R regulates IgE-dependent processes in human basophils and provides a novel function of the H4R preventing an overwhelming immune reaction by engagement of a negative feedback loop.

Cited by 31 publications

References 32 publications

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

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

Histamine H4 Receptor in Allergic Dermatitis

Important and specific role for basophils in acute allergic reactions

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