Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion

Abstract

Mast cells are involved in many disorders where the triggering mechanism that leads to degranulation and/or cytokine secretion has not been defined. Several chronic inflammatory diseases are associated with increased mast cell numbers and upregulation of the TNF receptor family member CD30, but the role of elevated CD30 expression is poorly understood. Here we report what we believe to be a novel way to activate mast cells with CD30 that leads to degranulation-independent secretion of chemokines. CD30 induced a de novo synthesis and secretion of the chemokines IL-8, macrophage inflammatory protein-1α (MIP-1α), and MIP-1β, a process involving the MAPK/ERK pathway. Mast cells were found to be the predominant CD30 ligand-positive (CD30L-positive) cell in the chronic inflammatory skin diseases psoriasis and atopic dermatitis, and both CD30 and CD30L expression were upregulated in lesional skin in these conditions. Furthermore, the number of IL-8-positive mast cells was elevated both in psoriatic and atopic dermatitis lesional skin as well as in ex vivo CD30-treated healthy skin organ cultures. In summary, characterization of CD30 activation of mast cells has uncovered an IgE-independent pathway that is of importance in understanding the entirety of the role of mast cells in diseases associated with mast cells and CD30 expression. These diseases include Hodgkin lymphoma, atopic dermatitis, and psoriasis.

A genome-wide association study of tick burden and milk composition in cattle

“…Several of these SNP were either in an exon or intron of a gene that had a known role in the adaptive immune system of mammals, or was within 50 kb of such a coding sequence. TNFSF8 (CD30) is a cytokine belonging to the tumour necrosis factor ligand family and has been shown to be upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion (Fischer et al 2006). SIRPA is a member of the immunoglobulin superfamily involved in the differentiation of monocytes to dendritic cells (Brooke et al 1998), the most potent antigen presenting cell, and has a known role in binding to CD47 (Oldenborg et al 2000).…”

Cytokines as potential biomarkers of liver toxicity induced by Dioscorea bulbifera L.

“…Recently, the interaction of CD30/CD30L was reported to play some role in the crosstalk between natural killer and dendritic cells, and is critical for humoral immunity (26,27). Meanwhile, some studies demonstrate that CD30L/CD30 might be useful as a novel biological therapy for allergic rhinitis, inflammatory bowel disease, autoimmune diabetes, and chronic inflammatory skin diseases like psoriasis or atopic dermatitis (28)(29)(30)(31). However, there is no report about whether there is some role of CD30L in liver injury.…”

The mast cell and allergic diseases: role in pathogenesis and implications for therapy

“…Beyond traditional signaling through the FceRI receptor on mast cells, a novel IgE-independent mast cell activation pathway has been proposed for AD involving CD30. Mast cells were shown to be the predominant CD30 ligand-positive cell in AD lesions and activation through CD30 induced a de novo synthesis and secretion of CXCL8, CCL3 and CCL4, via the extracellular-signal regulated kinase (ERK)/(Mitogenactivated protein kinase) MAPK pathway [91].…”