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Publication : Different toll-like receptor stimuli have a profound impact on cytokines required to break tolerance and induce autoimmunity.

First Author  Lin AC Year  2011
Journal  PLoS One Volume  6
Issue  9 Pages  e23940
PubMed ID  21931625 Mgi Jnum  J:177886
Mgi Id  MGI:5296437 Doi  10.1371/journal.pone.0023940
Citation  Lin AC, et al. (2011) Different toll-like receptor stimuli have a profound impact on cytokines required to break tolerance and induce autoimmunity. PLoS One 6(9):e23940
abstractText  Although toll-like receptor (TLR) signals are critical for promoting antigen presenting cell maturation, it remains unclear how stimulation via different TLRs influence dendritic cell (DC) function and the subsequent adaptive response in vivo. Furthermore, the relationship between TLR-induced cytokine production by DCs and the consequences on the induction of a functional immune response is not clear. We have established a murine model to examine whether TLR3 or TLR4 mediated DC maturation has an impact on the cytokines required to break tolerance and induce T-cell-mediated autoimmunity. Our study demonstrates that IL-12 is not absolutely required for the induction of a CD8 T-cell-mediated tissue specific immune response, but rather the requirement for IL-12 is determined by the stimuli used to mature the DCs. Furthermore, we found that IFNalpha is a critical pathogenic component of the cytokine milieu that circumvents the requirement for IL-12 in the induction of autoimmunity. These studies illustrate how different TLR stimuli have an impact on DC function and the induction of immunity.
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