Benzo[a]pyrene exposure causes exonal switch resulting in reduced surface CD5 expression in an AHR-dependent manner.

• CD5 is a pan T cell marker and regulate its development, function, and activation. • Expression of an alternative exon(E1B) directly downregulated its surface expression. • This study reports a poly aromatic hydrocarbon (BaP) induced and AHR mediated upregulation of E1B expression. • This increase in E1B expression could play an essential role in regulation of TCR activity thus contributing towards functional anomalies. • CD5 is a crucial surface receptor of T cells, whose expression majorly affects its development, function, and overall biology. • Expression of a Human Endogenous Retrovirus (HERV) originated exon (E1B) directly downregulates the surface expression of CD5. • This study reports a polycyclic aromatic hydrocarbon i.e. BaP, induced upregulation of E1B expression in an AHR dependent manner, leads to the reduction of CD5 surface expression. • This mechanism improves our understanding of an environmental pollutant induced deregulation of t cell activity in humans. The function of CD5 protein in T cells is well documented, but regulation of its surface-level expression has yet to be fully understood. However, variation in its surface expression is associated with various immunopathological conditions and haematological malignancies. Briefly, expression of an alternate exon E1B of a human endogenous retroviruses (HERV) origin directly downregulates the conventional transcript variant (E1A), as its expression leads to the retention of the resultant protein at the intracellular level (cCD5). A separate promoter governs the expression of E1B and may be influenced by different transcription factors. Hence, we performed in silico transcription factor binding site (TFBS) analysis of the 3 kb upstream region from TSS of exon E1B and found five putative DREs (Dioxin Response elements) with good similarity scores. Further, we observed the upregulation in E1B expression after the exposure of BaP (a dioxin) and the reduction of E1A expression and their respective protein, i.e. sCD5 and cCD5. The binding of AHR at the predicted DRE sites was confirmed by ChIP qPCR and AHR specific inhibitor and gene silencing studies suggested the involvement of AHR in exonal switch. This study indicates that the polycyclic aromatic hydrocarbon decreases the sCD5 expression by upregulating alternative exon expression, which may adversely affect the overall T cell functions. [ABSTRACT FROM AUTHOR]