SEX BIAS IN TLR - DEPENDENT RESPONSES : VARIATIONS ON THE X CHROMOSOME

Orateur : Jean-Charles GUERY (CPTP, Toulouse)

Toll-like receptor 7 (TLR7), an endosomal sensor of single-stranded RNA encoded on the X chromosome, is critical to the induction of antiviral immunity, but TLR7 dosage is also a key pathogenic factor in systemic lupus erythematosus (SLE), an autoimmune disease with strong female bias. In plasmacytoid dendritic cells (pDCs), TLR7 engagement elicits strong type I interferon production and is critical to the induction of antiviral immune responses. TLR7 is also an essential component of the germinal center response against RNA viruses. We have shown that the TLR7- driven production of type I IFNs by pDCs exhibits a strong female bias, due to the combined action of estrogen-signaling and X-chromosome dosage. We recently examined the functional impact of a frequent single nucleotide polymorphism of TLR7 and whether TLR7 escapes from X chromosome inactivation (XCI) in immune cells from women. Taken together, our results imply a direct effect of escape from XCI or sex-genotype interactions in the control of TLR7 protein dosage in women, affecting the functional responses of B cells and pDCs. These results illustrate the importance of the tight regulation of TLR7 expression in the control of immunity and suggest that sex-dependent regulation of TLR7 expression may account for the sex bias in SLE susceptibility, and contribute also to female-specific immunopathogenic traits in the response to HIV infection.

Télécharger dans mon agenda