b and t lymphocyte attenuator is a target of mir-155 during naive cd4+ t cell activation

background: microrna-155 (mir-155) is upregulated during t cell activation, but the exact mechanisms by which it influences cd4+ t cell activation remain unclear. objective: to examine whether the b and t lymphocyte attenuator (btla) is a target of mir-155 during naïve cd4+ t cell activation. methods: firefly luciferase reporter plasmids pezx-mt01-wild-type-btla and pezx-mt01-mutant-btla were constructed. lymphocytes were nucleofected with mir-155 inhibitor or negative control (nc). then, naïve cd4+ cd62l+ helper t cells purified from lymphocytes were stimulated with immobilized antibody to cd3 and soluble antibody to cd28. mir-155 and btla expression were examined by real-time rt-pcr. cell surface cd69 expression and il-2 secretion were measured by elisa and flowcytometry, respectively. results: luciferase reporter assay showed that mir-155 targeted the btla 3’utr region. compared with non-stimulated condition, both mir-155 and btla mrna expression were upregulated after t cell activation. similar results were observed for blta protein expression. compared with nc, the mir-155 inhibitor decreased mir-155 by about 45%, but did not influence btla mrna expression. compared with nc, the mir-155 inhibitor decreased the surface btla expression by about 60%. upregulation of btla in mir-155 knockdown cd4+ t cells did not influence the cell surface expression of cd69, an early activation marker (p=0.523). similarly, il-2 production was not changed. conclusion: mir-155 is involved in the inhibition of btla during cd4+ t cell activation. these results might serve as a basis for an eventual therapeutic manipulation of this pathway to treat inflammatory and autoimmune diseases.