A77 1726, the active metabolite of leflunomide, attenuates lupus nephritis by promoting the development of regulatory T cells and inhibiting IL-17-producing double negative T cells
Lupus nephritis (LN) is a challenging problem that affects 50% of patients with systemic lupus erythematosus (SLE) without effective therapy. Here, we report that A77 1726, the active metabolite of leflunomide, effectively inhibits development of LN and attenuates the generalized autoimmune features. A77 1726 suppresses the expansion of double negative (DN) T cells, and inhibits T and B cell activation. Intriguingly, A77 1726 treatment significantly increases CD4(+)Foxp3(+) regulatory T cells but suppresses potential "pathogenic" IL-17-producing DN T cells in lymph nodes. In vitro experiment shows that A77 1726 potentiates the conversion of naive CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(+) inducible regulatory T cells (iTregs) by inhibiting Akt. Taken together, our data indicate that the therapeutic effects of A77 1726 in murine LN are mediated, at least in part, by augmenting iTregs which suppress pathogenic IL-17-producing DN T cells through an Akt-dependent mechanism.
Pharmacology, Toxicology and Pharmaceutical Science
2
9%
Agricultural and Biological Sciences
2
9%
Immunology and Microbiology
1
4%
Energy
1
4%
Other
2
9%
Unknown
10
43%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 13. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 July 2026.
All research outputs
#3,669,683
of 34,089,221 outputs
Outputs from Clinical Immunology
#235
of 2,580 outputs
Outputs of similar age
#43,044
of 411,620 outputs
Outputs of similar age from Clinical Immunology
#6
of 28 outputs
Altmetric has tracked 34,089,221 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,580 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one has done particularly well, scoring higher than 90% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 411,620 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 28 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.
