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. Author manuscript; available in PMC: 2017 Jan 1.
Published in final edited form as: Transl Res. 2015 Apr 29;167(1):214–227. doi: 10.1016/j.trsl.2015.04.011

Figure 3. Model.

Figure 3

Model mechanism for age-dependent decline in T1D susceptibility. Studies support the existence of an elevated innate inflammatory state associated with T1D susceptibility in human T1D families and diabetic rat models. In human T1D families, this state is independent of HLA, autoantibody status and disease progression. In BBDR rats, this state is independent of the MHC, insulitis and disease progression, but is associated with the ability of KRV to trigger disease progression. This inflammatory state may be the consequence of genetics, diet and intestinal microbiome. We further hypothesize that this heightened inflammatory state represents a “fertile field” in which the additive inflammation mediated through viral infection can lead to the breaking of immunological tolerance and the progression of autoimmunity in susceptible hosts. Our studies support that this heightened underlying inflammatory state is subsequently supplanted by induction of an immunoregulatory state over time. As these endogenous regulatory processes become more robust, the immune balance makes environmental triggering of T1D progression less likely.