IK Induced by Coxsackievirus B3 Infection Transiently Downregulates Expression of MHC Class II Through Increasing cAMP

Abstract

Major histocompatibility complex (MHC) class II expression is critical for the presentation of antigens in the immune response to viral infection. Consequently, some viruses regulate the MHC class II-mediated presentation of viral antigens as a mechanism of immune escape. In this study, we found that Coxsackievirus B3 (CVB3) infection transiently increased IK expression, which reduced the expression of MHC class II (I-A/I-E) on splenic B cells. Interestingly, CVB3-induced IK elevated cAMP, a downstream molecule of the G protein-coupled receptors, which inhibited MHC class II presentation on B cells. Transgenic mice expressing truncated IK showed lower expression of MHC class II on B cells than did wild-type mice after CVB3 infection. Taken together, these results imply that IK plays a role in downregulating MHC class II expression on B cells during CVB3 infection through the induction of cAMP.

IK acts as an immunoregulator of inflammatory arthritis by suppressing TH17 cell differentiation and macrophage activation

“…To investigate the potential of tIK cytokine in RA, we generated a crossbred mouse by breeding a tIK-expressing transgenic (termed tIK-Tg) mouse12 and an IL-1 receptor antagonist knockout (termed IL1RaKO) mouse on the BALB/c background131415. This crossbred mouse was designated tIK-IL1RaKO (Fig.…”

“…tIK transgenic mice were generated as previously described12. IL-1 receptor antagonist knockout (IL1RaKO) mice on the BALB/c background were kindly provided by M. L. Cho (Catholic Research Institute of Medical Science, The Catholic University of Korea, Korea).…”

“…The IK cytokine harvested from the supernatant of K562 was truncated to a 19-kd protein (truncated IK, tIK cytokine), which was translated from the methionine 316 residue of the full-length IK cytokine without the nuclear localization sequence10. This tIK cytokine still functioned effectively in downregulation of MHC class II expression, similarly to the full-length IK cytokine1112. Moreover, it protected against systemic lupus erythematosus pathogenesis by reducing MHC class II expression and anti-DNA antibodies11.…”

“…Moreover, it protected against systemic lupus erythematosus pathogenesis by reducing MHC class II expression and anti-DNA antibodies11. Recently, we reported that coxsackievirus B3 (CVB3), which can induce systemic activation of most immune cells, producing a cytokine storm, transiently induced IK cytokine expression and was also able to downregulate expression of MHC class II on B cells by increasing cAMP12. Based on these reports, it can be speculated that tIK cytokine may regulate excessive activation of immune cells.…”

Therapeutic Effect of Exogenous Truncated IK Protein in Inflammatory Arthritis

“…In addition, we reported that Coxsackievirus B3 (CVB3) infection transiently induced IK mRNA and that the expressed IK protein bound to G protein-coupled receptors and increased cyclic AMP (cAMP) levels in cytoplasm, and that this CVB3-IK-cAMP axis was the cellular mechanism behind the previous observation that CVB3 infection reduced MHC class II expression in myocytes [ 5 ]. Therefore, induction of IK might be a survival strategy of CVB3 to escape host immune responses [ 6 ].…”