Effect of tumor necrosis factor-α induced protein 8 like-2 on immune function of dendritic cells in mice following acute insults

Abstract

// Ying-yi Luan 1,2,* , Ren-qi Yao 3,* , Sen Tong 2 , Ning Dong 2 , Zhi-yong Sheng 2 and Yong-ming Yao 2,4 1 Medical School of Chinese PLA, The Chinese PLA General Hospital, Beijing, People’s Republic of China 2 Trauma Research Center, First Hospital Affiliated to The Chinese PLA General Hospital, Beijing, People’s Republic of China 3 10th Student Team, Undergraduate Medical School, Second Military Medical University, Shanghai, People’s Republic of China 4 State Key Laboratory of Kidney Disease, The Chinese PLA General Hospital, Beijing, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Yong-ming Yao, email: // Keywords : dendritic cells, tumor necrosis factor-α induced protein 8 like-2, maturation, differentiation, Immunology and Microbiology Section, Immune response, Immunity Received : December 12, 2015 Accepted : March 18, 2016 Published : March 28, 2016 Abstract Tumor necrosis factor-α induced protein 8 like-2 (TNFAIP8L2, TIPE2) is a lately discovered negative regulator of innate immunity and cellular immunity. The present study was designed to investigate whether naturally occurring dendritic cells (DCs) could express TIPE2 mRNA/protein and its potential significance. Expressions of co-stimulatory molecules on DC surface and cytokines were analyzed to assess the functional role of TIPE2 in controlling DC maturation as well as activation. The activated DCs were assessed for their capacity to stimulate the proliferation and differentiation of T cells. It was found that TIPE2 was a cytoplasmic protein expressed in DCs, and the percentage of DCs which expressed co-stimulatory molecules and cytokines were obviously up-regulated when TIPE2 gene silenced by siRNA in vitro and in vivo . DCs undergone TIPE2 knockdown were found to promote the maturation of DCs, T-cell proliferation as well as differentiation, and they were significantly elevated IL-2 level and intranuclear NF-AT activation. Conversely, in over-expressing TIPE2 DC cells, it could inhibit T-cell proliferation and differentiation, and markedly down-regulate IL-2 expression and intranuclear NF-AT activation after scald injury. The results suggested that TIPE2 appeared to be a critical immunoregulatory molecule which affected DC maturation and subsequent T-cell mediated immunity.