The killer-cell Ig-like receptor (KIR) 2DL4 (CD158d) acts as a receptor for human leukocyte antigen (HLA)-G and is expressed on almost all human natural killer (NK) cells. The expression and function of KIR2DL4 in other hematopoietic cells is poorly understood. Here, we focused on human mast cells, which exhibit cytotoxic activity similar to that of NK cells. KIR2DL4 was detected in all examined human cultured mast cells established from peripheral blood derived from healthy volunteers (PB-mast), the human mast cell line LAD2, and human nonneoplastic mast cells, including those on pathologic specimens. An agonistic antibody against KIR2DL4 decreased KIT-mediated and IgE-triggered responses, and enhanced the granzyme B production by PB-mast and LAD2 cells, by activating Src homology 2-containing protein tyrosine phosphatase (SHP-2). Next, we performed a coculture assay between LAD2 cells and the HLA-G þ cancer cells, MCF-7 and JEG-3, and showed that KIR2DL4 on LAD2 cells enhanced MMP-9 production and the invasive activity of both cell lines via HLA-G. Immunohistochemical analysis revealed that the direct interaction between HLA-G þ breast cancer cells and KIR2DL4 þ tissue mast cells (observed in 12 of 36 cases; 33.3%) was statistically correlated with the presence of lymph node metastasis or lymphvascular invasion (observed in 11 of 12 cases; 91.7%; x 2 ¼ 7.439; P < 0.01; degrees of freedom, 1) in the clinical samples. These findings suggest that the KIR2DL4 on human mast cells facilitates HLA-G-expressing cancer invasion and the subsequent metastasis.

PD-1 could be a marker for human cutaneous mastocytosis and regulate the growth of human PD-1-positive mastocytosis cells.

Gastrointestinal schwannomas and schwannomas with peritumoral lymphoid cuffs may be associated with elevated FDG uptake. Knowledge of the features of schwannomas associated with increased uptake may be helpful to avoid misinterpretation of benign schwannomas as malignancy.

Lupus erythematosus profundus (LEP) is a variant of lupus erythematosus, involving the deep dermis and subcutaneous fat. LEP is characterized by the presence of lymphoid follicles (LF) and germinal centers (GC). However, it remains unknown whether these lymphoid structures correspond to the lymphoid tissues such as cutaneous tertiary lymphoid organs (TLO). Previously, we identified dynamically orchestrated cellular elements in murine contact dermatitis that resembled lymphoid structures, which we termed inducible skin-associated lymphoid tissues (iSALT). We subsequently reported structures analogous to iSALT in human secondary syphilis, suggesting that iSALT can also exist in humans. Here, we studied ectopic lymphoid tissues in the lesions of LEP by immunohistochemistry and compared their characteristics with those of TLO. We demonstrated that LF of LEP were composed of B-cell follicles intermingled with CXCL13-expressing cells, distinct aggregations of T cells, and some blood vessels expressing peripheral node addressin. These findings indicate that LF of LEP can be considered as a type of iSALT.