Journal
IMMUNITY
Volume 29, Issue 6, Pages 899-911Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2008.10.011
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Funding
- National Institutes of Health [R01 HL-62215]
- Lupus Research Institute
- Alliance for Lupus Research
- National Multiple Sclerosis Society
- American Heart Association
- SLE Lupus Foundation Fellowship
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The T helper 17(Th17) cell lineage is important in inflammatory and autoimmune responses, via its ability to produce interleukin-17 (IL-17) and IL-21. Given the potentially deleterious effects of Th17 cells, their generation needs to be strictly controlled. IRF-4 is a transcription factor that has recently emerged as a key regulator of Th17 cell differentiation. Here, we showed that mice deficient in a previously isolated protein, IBP (IRF-4-binding protein), rapidly developed rheumatoid arthritis-like joint disease and large-vessel vasculitis. The pathology was associated with an enhanced responsiveness of T cells to low levels of stimulation and with the inappropriate synthesis of IL-17 and IL-21. IBP sequestered IRF-4 and prevented it from targeting the transcriptional regulatory regions of the genes that encode IL-17 and IL-21. Thus, IBP appears to be important in preventing T cell-mediated autoimmunity by ensuring that the production of IL-17 and IL-21 does not occur in response to self-antigens.
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