Figure 1.

The pathway to xenobiotic-induced autoimmunity. We propose that xenobiotic tissue damage can lead to the availability of nucleic acids and other damage associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs), the release of self- and modified self-antigens, the presentation of self-antigens to non-tolerant lymphocytes, and the induction of inflammation. Such effects lead to the engagement of TLRs and other innate sensors, the production of inflammatory cytokines, the contraction of T regulatory cell populations, the expansion of autoreactive B and T effector-cell populations, and the production of autoantibodies. These events can occur at the site of exposure such as the lungs where they occur in ELS or in SLO. In either case the expansion of autoreactive cells and their migration to target tissues such as the kidney in SLE results in autoimmune disease. SLO, secondary lymphoid organ; ELS, ectopic lymphoid structures; IFN, interferons; TNF, tumor necrosis factor; IL, interleukin; T_eff, effector T cell; T_R, T regulatory cell; aT, autoreactive T cell; aB, autoreactive B cell; DC, dendritic cell.