ArticlePloS one2011
CD4+FoxP3+ regulatory T cells from Gαi2-/- mice are functionally active in vitro, but do not prevent colitis.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed.
- Loss of GαScientific reports · 2017Article
- Elevated fecal peptidase D at onset of colitis in Galphai2-/- mice, a mouse model of IBD.PloS one · 2017Article
- Implications of non-canonical G-protein signaling for the immune system.Cellular signalling · 2014Review
- Diagnosis and management of microscopic colitis: current perspectives.Clinical and experimental gastroenterology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMice deficient in the inhibitory G protein subunit Gαi2 spontaneously develop a T helper 1 dominated colitis. We examined whether a defect in CD4(+)FoxP3(+) regulatory T cells (Treg) underpins the pathogenesis of colitis in the Gαi2(-/-) (Gαi2-deficient) colitis model. METHODOLOGY/PRINCIPAL
findingsUsing flow cytometry, we found that thymus and colonic lamina propria, but not spleen and mesenteric lymph nodes, of colitic Gαi2(-/-) mice contained increased frequencies of Treg, whereas FoxP3 expression intensity was similar in Gαi2(-/-) compared to Gαi2(+/-) or Gαi2(+/+) wild type (WT) mice. The frequency of CD4(+)FoxP3(+) T cells expressing CD103 was significantly increased in Gαi2(-/-) compared to WT mice. Treg in colons from WT mice clustered in the T cell areas of colonic lymphoid patches (CLP), with relatively few Treg in the lamina propria, as demonstrated by immunohistochemistry. In Gαi2(-/-) mice, CLP were not observed but lamina propria Treg were increased in number and frequency within the CD4(+) infiltrate, compared to WT mice. Using an in vitro co-culture system and flow cytometric analysis of cell division we could demonstrate that the in vitro suppressive function of WT and Gαi2(-/-) CD4(+)FoxP3(+) regulatory T cells (WT-Treg and KO-Treg) was indistinguishable, but that T effector cells (CD4(+)25(-) T cells) from Gαi2(-/-) mice were less readily suppressed than WT effectors (WT-Teff) by Treg from either source. However, neither WT nor Gαi2(-/-) Treg was able to suppress colitis induced by adoptive transfer of Gαi2(-/-) effector T cells (KO-Teff) to RAG2(-/-) recipients. The enhanced inflammatory activity of Gαi2(-/-) effectors was accompanied by increased expression of an effector/memory T cell phenotype and increased cytokine secretion, especially IL-4, IL-6 and IFN-γ.
conclusionsThere is an increased frequency of Gαi2(-/-) Treg in the colon, and they demonstrate no endogenous functional defect. However, Gαi2(-/-) T effector cells are dramatically less susceptible to suppression in vitro, and in vivo, despite increased effective numbers of Treg, they cannot prevent disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.