Jin Kyeong Choi1 *, Jun-Young Park2 *, Soyoung Lee,3 Young-Ae Choi,4 Song Kwon,2 Min Jun Shin,2,5 Hui-Suk Yun,6 Yong Hyun Jang,7 Jinjoo Kang,4 Namkyung Kim,4 Dongwoo Khang,2,5,8 Sang-Hyun Kim4 1Department of Immunology, Jeonbuk National University Medical School, Jeonju, 54907, Republic of Korea1; 2Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, Republic of Korea; 3Immunoregulatory Materials Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, 56212, Republic of Korea; 4CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea; 5Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 21999, Republic of Korea; 6Powder & Ceramics Division, Korea Institute of Materials Science, Changwon, 51508, Republic of Korea; 7Department of Dermatology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea; 8Department of Physiology, School of Medicine, Gachon University, Incheon, 21999, Republic of Korea*These authors contributed equally to this workCorrespondence: Dongwoo Khang, Department of Physiology, School of Medicine, Gachon University, Incheon, 21999, Republic of Korea, Tel +82 32 899 6515, Email dkhang@gachon.ac.kr Sang-Hyun Kim, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea, Tel +82 53 420 4838, Email shkim72@knu.ac.krPurpose: The protein corona surrounding nanoparticles has attracted considerable attention as it induces subsequent inflammatory responses. Although mesoporous silica nanoparticles (MSN) are commonly used in medicines, cosmetics, and packaging, the inflammatory effects of the MSN protein corona on the cutaneous system have not been investigated till date.Methods: We examined the greater plasma protein adsorption on MSN leads to serious inflammatory reactions in Dermatophagoides farinae extract (DFE)-induced mouse atopic dermatitis (AD)-like skin inflammation because of increased uptake by keratinocytes.Results: We compare the AD lesions induced by MSN and colloidal (non-porous) silica nanoparticles (CSN), which exhibit different pore architectures but similar dimensions and surface chemistry. MSN-corona treatment of severe skin inflammation in a DFE-induced in vivo AD model greatly increases mouse ear epidermal thickness and infiltration of immune cells compared with the CSN-corona treatment. Moreover, MSN-corona significantly increase AD-specific immunoglobulins, serum histamine, and Th1/Th2/Th17 cytokines in the ear and lymph nodes. MSN-corona induce more severe cutaneous inflammation than CSN by significantly decreasing claudin-1 expression.Conclusion: This study demonstrates the novel impact of the MSN protein corona in inducing inflammatory responses through claudin-1 downregulation and suggests useful clinical guidelines for MSN application in cosmetics and drug delivery systems.Graphical Abstract: Keywords: protein Corona, atopic dermatitis, mesoporous silica, colloidal silica, claudin-1, immunotoxicity