IL-24 contributes to skin inflammation in Para-Phenylenediamine-induced contact hypersensitivity
SCIENTIFIC REPORTS
Authors: Van Belle, Astrid B.; Cochez, Perrine M.; de Heusch, Magali; Pointner, Lisa; Opsomer, Remi; Raynaud, Peggy; Achouri, Younes; Hendrickx, Emilie; Cheou, Pamela; Warnier, Guy; Renauld, Jean-Christophe; Baeck, Marie; Dumoutier, Laure
Abstract
Para-Phenylenediamine (PPD) is an aromatic amine used in hair dyes and in temporary black henna tattoos, which is a frequent cause of allergic contact dermatitis (ACD). ACD is a skin inflammatory reaction characterized by modifications such as spongiosis, exocytosis and acanthosis. The aim of this study is to characterize the expression and the role of IL-20-related cytokines, including IL-19, IL-20, IL-22 and IL-24, in ACD. The expression of IL19, IL20, IL22 and IL24 is increased in affected skin from PPD allergic patients compared with uninvolved skin. In addition, the expression of these cytokines positively correlates with clinical symptoms. To assess their role in ACD, we set up a mouse model of PPD-induced allergic contact dermatitis and we showed that, in contrast to Il22-deficient mice, Il22ra1-, Il20rb- and Il24-deficient mice are partially protected against development of PPD-induced contact hypersensitivity. These mice have decreased ear thickening and less acanthosis compared with WT mice after PPD treatment. In addition, the absence of IL-22R, IL-20R2 or IL-24 affects the recruitment of neutrophils into the skin but not the total IgE production. Taken together, these results demonstrate the implication of IL-24 via the IL-20R type II receptor in the inflammatory process of ACD.
MUC1 as a target for CAR-T therapy in head and neck squamous cell carinoma
CANCER MEDICINE
Authors: Mei, Zi; Zhang, Kai; Lam, Alfred King-Yin; Huang, Junwen; Qiu, Feng; Qiao, Bin; Zhang, Yi
Abstract
The modification of chimeric antigen receptor (CAR) endowing T cells with tumor-specific cytotoxicity induces antitumor immunity. However, the structural characteristics of solid tumors, the loss of specific antigens, and the strong immunosuppressive environment are challenges to treat solid tumors with CAR-T therapy. The purpose of our study was to find and verify the potentials of CAR-T therapies for patients with head and neck squamous cell carcinoma (HNSCC). First, we selected MUC1 as our research target and verified its differential expression in cancer tissues and adjacent non-neoplastic tissues (ANNT). Next, we constructed a second-generation CAR and validated the cytotoxic function in vitro. In our study, we found that exogenous addition human IL22 recombinant protein could increase the MUC1 expression and enhance the function of T cells. In addition, we constructed a fourth-generation CAR that secretes IL22. Finally, we verified the antitumor function of two different CAR-T cells in vitro and in vivo, respectively. CAR-MUC1-IL22 T cells were found to have a stronger and more effective cytotoxic function against MUC1 + HNSCC cells. Taken together, these results demonstrate the potential effectiveness of CAR-T in the treatment of patients with HNSCC and provide evidence-based of MUC1 + CAR-T therapy.