Signals from the TAFA4-PTEN-PU.1 axis alleviate nasal allergy by modulating the expression of FcεRI in mast cells.

The high-affinity IgE receptor, FcεRI, plays a key role in the antigen-induced mast cell activation. Regulations for FcεRI are not yet well understood. TAFA4 is a molecule derived from neuron tissues, and has immune regulation functions. This study aims to clarify the role of TAFA4 in the regulation of FcεRI expression in mast cells. Nasal secretions were collected from patients with allergic rhinitis (AR) and healthy control (HC) subjects. TAFA4 levels of nasal secretions were evaluated by ELISA. A mouse model AR was developed using ovalbumin as the specific antigen. Negative correlation between TAFA4 and tryptase levels in nasal secretions was observed. TAFA4 could suppress the antigen-related mast cell activation. TAFA4 modulated the transcription of Fcer1g (FcεRI γ gene) in mast cells. Signals from the TAFA4-PTEN-PU.1 axis restricted FcεRI expression in mast cells. Administration of TAFA4 attenuated experimental AR. TAFA4 suppressed the expression of FcεRI in mast cells of airway tissues. TAFA4 can down regulate the expression of FcεRI in mast cells to suppress experimental AR. The data suggest that TAFA4 has translation potential to be developed as an anti-allergy therapy.

Identification of antigen-specific neutrophils in the tonsils with recurrent acute inflammation.

The pathogenesis of recurrent acute tonsillitis (Rtn) is to be further investigated. Polymorphonuclear neutrophils (PMN) often associate with the pathogenesis of acute and chronic inflammation. This study aims to identify the antigen-specific PMNs (sPMNs) isolated from the tonsillar tissues with recurrent acute inflammation. In this study, CD66b+ PMNs were isolated from surgically removed tonsils (40 tonsils were from 20 Rtn patients; 24 tonsils were from 12 tonsil tumour patients) by flow cytometry cell sorting. sPMNs were identified through immunological approaches. We found that compared with the control tonsil samples (from marginal non-tumour tissues of tonsil cancer), Rtn samples showed higher PMN frequency, higher levels of myeloperoxidase (MPO) and neutrophil elastase (NE), in which positive correlation was detected between the inflammatory scores in the Rtn tissues and PMN counts (r = .7352; p = .0002), or MPO (r = .6565, p = .0017), or NE (r = .6687, p = .0013). Upon exposure to tonsillar tissue protein extracts in the culture, a portion of Rtn PMNs was activated and released inflammatory mediators. A complex of tonsillar tissue-specific IgG and FcγRI was observed on the surface of Rtn PMNs; these PMNs could specifically recognize the Rtn tissue extracts and were designated the tonsillar antigen-specific PMNs (sPMNs). A signal transduction pathway of mitogen-activated protein kinase (MAPK)-nuclear factor of T cell activation (NFAT) was activated in sPMNs after exposure to Rtn tissue extracts. In summary, a fraction of sPMN in the Rtn tonsillar tissues was identified and characterized. The sPMNs can be activated upon exposure to tonsil-specific antigens. These sPMNs may contribute to the Rtn pathogenesis.