Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: NAC1 Modulates Autoimmunity by Suppressing Regulatory T Cell- Mediated Tolerance FoxP3+ regulatory T cells (Tregs) are a distinct subset of CD4+ T cells integral to the maintenance of the balance of the immune system, and their dysregulation is a trigger of autoimmunity. We report here that nucleus accumbens-associated protein-1 (NAC1), a nuclear factor of the broad complex, tramtrack, bric-a-brac / poxvirus and zinc finger (BTB/POZ) gene family, is a negative regulator of FoxP3 in Tregs and a critical determinant of immune tolerance. Phenotypically, NAC1-/- mice show substantial tolerance to the induction of autoimmunity, as evidenced by the significantly decreased occurrences of autoimmune arthritis and colitis. Analysis of T cells from the wild-type (WT) or NAC1 knockout (-/-) mice found that NAC1 is crucially involved in the early stage of T cell development. NAC1 positively affects CD8+ T cell differentiation, but negatively regulates Treg development. Compared with WT animals, NAC1-/- mice displayed defects in CD8+ T cell development but generated a larger amount of CD4+ regulatory Tregs that exhibit a higher metabolic profile and immune suppressive activity, increased acetylation, and expression of FoxP3, and slower turnover of this transcriptional factor. Furthermore, treatment of Tregs with the pro-inflammatory cytokines IL-1{beta} or TNF- induced a robust upregulation of NAC1 but an evident downregulation of FoxP3 as well as the acetylated FoxP3, suggesting that the reduction of FoxP3 by the NAC1-mediated deacetylation and destabilization of this lineage-specific transcriptional factor contributes considerably to break of immune tolerance. These findings imply that the pro-inflammatory cytokines-stimulated upregulation of NAC1 acts as a trigger of the immune response through destabilization of Tregs and suppression of tolerance induction, and that therapeutic targeting of NAC1 warrants further exploration as a potential tolerogenic strategy for treatment of autoimmune disorders.
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The categories of this paper are: education
15
The categories of this paper are: developmental
13
The categories of this paper are: animal
19
The categories of this paper are: epidemiology
14
The categories of this paper are: biophysics
32
The categories of this paper are: zoology
0
The categories of this paper are: genetics
1
The categories of this paper are: bioinformatics
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The categories of this paper are: ecology
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The categories of this paper are: neuroscience
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The categories of this paper are: microbiology
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The categories of this paper are: evolutionary
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The categories of this paper are: pharmacology
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The categories of this paper are: synthetic
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The categories of this paper are: paleontology
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The categories of this paper are: cancer