NKp46 regulates the production of serine proteases and IL‐22 in human mast cells in urticaria pigmentosa

Abstract

NKp46 (natural cytotoxic receptor 1/CD335) is expressed on natural killer cells and Th2-type innate lymphocytes. However, NKp46 expression in human mast cells has not yet been reported. Here, we explored the expression of, and possible role played by, NKp46 in such cells. NKp46 protein was expressed in human mast cells in urticaria pigmentosa principally of the tryptase-positive/chymase-negative type (MCT), but not in human non-neoplastic skin mast cells of the tryptase-positive/chymase-positive (MCTC) type. NKp46 expression was also evident in the human neoplastic mast cell line HMC1.2. NKp46 knockdown changed the phenotype of this cell line from MCT to MCTC and downregulated GrB production, but did not influence IL-22 production. An agonistic anti-NKp46 antibody upregulated production of GrB and IL-22, but did not change the MCT-like phenotype of HMC1.2 cells. NKp46 was thus involved in the production of serine proteases and IL-22 in human mast cells.

Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis

“…Studies using mast cell-deficient mice, such as Kit W/Wv mice and Kit Wsh/Wsh mice, revealed that mast cells protect against parasitic infections including Strongyloides ratti and Strongyloides brasiliensis [7,8], as well as the venoms of honeybees or vipers [9]. Mast cells are (KIR) 2DL4 [19][20][21][22][23][24][25][26][27][28][29][30][31]. These include inhibitory receptors characterized by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) within their cytosolic domains ( Figure 1) [32].…”

Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells Both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis

“…KIT-mediated and IgE receptor-mediated responses in mast cells can be modified by other receptors expressed on the cell surface. These include inhibitory receptors [7][8][9][10][11][12][13][14][15][16][17] characterized by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) within their cytosolic domains [18]. ITIMs comprise the homology sequence In previous work, we identified the expression in human mast cells of the inhibitor receptor killer inhibitory receptor (KIR) 2DL4 (CD158d) [16,17].…”

SLAM family member 8 is involved in oncogenic KIT‐mediated signalling in human mastocytosis

“…Therefore, inhibition of KIT signalling would be useful when treating this neoplastic disorder . A promising means to this end is stimulation or blocking of receptors expressed by human mastocytosis cells . Another SLAM family member CD84 would be also a promising target to inhibit KIT signalling.…”