Selenoprotein K (SelK) is an 11-kDa selenoprotein, which may be involved in the regulation of oxidative stress, endoplasmic reticulum (ER) stress and immune response. To explore the function of SeIK in the process of immune response, several short-hairpin RNAs (shRNA) were designed for the construction of recombinant plasmids to down-regulate the expression of SeIK gene in vitro. These shRNAs specifically and efficiently interfered with the expression of SelK at both mRNA and protein levels. The expression of calcium homoeostasis endoplasmic reticulum protein (CHERP) and the intracellular free Ca2+ concentration were significantly down-regulated in anti-CD3 stimulated SelIC-knockdown cells. The expression of Interleukin 2 receptor alpha chain (IL-2R alpha) and the secretion of Interleukin 4 (IL-4), which play a significant role in the process of T cell activation and proliferation, were also reduced in SeIK-knockdown cells. Selenomethionine (Se-Met) at an optimum concentration of 5 mu M could up-regulate SelK expression and reverse the change of the expression of CHERP and the intracellular free calcium caused by SelICknockdown. These results hereby imply SelK may regulate the release of Ca2+ by CHERP and play an important role in the proliferation and differentiation of T cell by TCR stimulation. (C) 2017 Elsevier Inc. All rights reserved.