Six new prenylated hydroquinones named ganocalidin A–F (1–6) and two new compounds of ganocalicine A (7) and B (8), together with sixteen known compounds (9–24) were isolated from an EtOAc extract of the fruiting body of Ganoderma calidophilum. The new compound structures were elucidated on the basis of spectroscopic data analysis including 1D, 2D NMR and MS. Compounds 1 and 7 showed inhibitory activity effects on β-hexosaminidase activity (IC₅₀ 9.44 and 9.14 μM, respectively), and significantly reduced the production of IL-4 and LTB₄ by RBL-2H3 cells in response to antigen stimulation, suggesting that 1 and 7 possess anti-allergic activity.

Dendritic cells (DCs) that express T cell immunoglobulin domain molecule-4 (TIM4), a cell surface receptor for phosphatidylserine, induce T helper 2 (T _H 2) cell responses and allergic reactions. We elucidated the role of the transcription factor X-box–binding protein-1 (XBP1) in the induction of the T _H 2 cell response through its role in generating TIM4 ⁺ DCs. We found that XBP1 was required for TIM4 mRNA and protein expression in airway DCs in response to the cytokine interleukin-2 (IL-2) and that this pathway was required for TIM4 expression on DCs in response to the allergens PM2.5 and Derf1. The IL-2–XBP1–TIM4 axis in DCs contributed to Derf1/PM2.5-induced, aberrant T _H 2 cell responses in vivo. An interaction between the guanine nucleotide exchange factor Son of sevenless-1 (SOS1) and the GTPase RAS promoted XBP1 and TIM4 production in DCs. Targeting the XBP1-TIM4 pathway in DCs prevented or alleviated experimental airway allergy. Together, these data suggest that XBP1 is required for T _H 2 cell responses by inducing the development of TIM4 ⁺ DCs, which depends on the IL-2–XBP1–SOS1 axis. This signaling pathway provides potential therapeutic targets for the treatment of T _H 2 cell–dependent inflammation or allergic diseases.

Skewed T helper 2 (Th2)‑cell polarization plays a critical role in the pathogenesis of allergic inflammations; however, the underlying mechanisms require further elucidation. The aim of the present study was to investigate the mechanisms through which the interaction between T‑cell immunoglobulin and mucin domain (TIM)4 and TIM1 regulates the expression of silent information regulator 1 (SIRT1) in Th2 cells, and the role of SIRT1 in Th2‑cell polarization during nasal allergic inflammation. The results demonstrated that TIM4 expression by splenic dendritic cells was increased in mice with allergic rhinitis, and the TIM4̸TIM1 interaction promoted CD4+ T cells to express SIRT1 during allergic inflammation via enhancing phosphoinositide 3‑kinase/Akt phosphorylation. SIRT1 then facilitated CD4+ T‑cell proliferation through downregulating the expression of Fas ligand, caspase-3 and p53 in mice with nasal allergic inflammation. In conclusion, the interaction of TIM4̸TIM1 was found to promote Th2‑cell proliferation through enhancing SIRT1 expression in mice with nasal allergic rhinitis.