#foxp3

Explore the Daily Current Affairs 7 October 2025, relevant for UPSC exam. Also download quick REVISION NOTES. Source: The Hindu newspaper (Page no. 6) Health concerns Context: Tamil Nadu Drugs Control Department found diethylene glycol (DEG), a toxic substance, above permissible limits in a sample of cough syrup which was linked to the deaths of at least 14 children in Rajasthan and Madhya…

Nature Immunology, Published online: 30 June 2025; doi:10.1038/s41590-025-02213-8 FOXP3 dependence Summary A new study published in Nature Immunology reveals a crucial dependency on the transcription factor FOXP3 for the sustained suppressive function of regulatory T cells (Tregs). The research, conducted in a mouse model of autoimmune diabetes, demonstrates that transient depletion of FOXP3,…

Gli acidi biliari hanno origine nel fegato, vengono immagazzinati nella cistifellea e infine rilasciati nell’intestino, dove vengono utilizzati per favorire la digestione dopo il consumo di un pasto. I microbi nel nostro intestino metabolizzano gli acidi biliari prodotti dal fegato, trasformandoli in una vasta gamma di molecole diverse chiamate acidi biliari secondari, che tendono ad essere più…

If you want to find out how your immune system reacts to a certain disease, an important first step is to identify the type of immune cells that are activated in that case. The immune system is incredibly complex, but it can be broken down into two types of T cells: T helper cells and T suppressor cells. If you want to learn more about these cell types and the diseases they can cause, then a foxp3 staining kit may be exactly what you need in your research laboratory! Read on to learn how this useful kit works and how it can help you carry out your next immunology experiment with ease!

What you get?

The Foxp3 staining kit includes everything you need to identify, quantify, and investigate Tregs in your studies. The included manual walks you through staining human and mouse samples, then transferring them onto a microscope slide for observation under different light wavelengths. When used correctly, it will allow you to visualize (and count) both CD4+ and CD8+ T cells that express FOXP3. You can even stain cryopreserved cells or tissue sections from stored formalin-fixed tissues!

How it works?

The Foxp3 staining kit contains everything you need to stain CD4+ CD25+ T regulatory cells (Tregs) and measure their frequency in peripheral blood samples. While a number of commercial antibodies exist for quantifying Tregs, staining for FOXP3 is preferred because it shows greater specificity, sensitivity, and accuracy. The kit contains all of the reagents needed to stain 20–50 sample wells.

Why use it?

There are many studies that try to analyze and characterize innate immune cells in order to see if they can be reprogrammed into Tregs. However, most of these studies require special flow cytometry methods in order to identify and quantify them (i.e., CD4+CD25+FoxP3). But not everyone has access to these kinds of high-end systems, so researchers who lack them are forced to look for workarounds.

The risks of not using it

When performing research using animal models, it’s common to need to assess whether or not certain immune cells are present in certain regions of a subject’s body. Most researchers take care of these tasks by hand, which can be time-consuming and difficult for graduate students and other lab members who might not have experience immunological techniques. Additionally, lack of proper training can lead to errors—and these mistakes could lead you to false conclusions or improper results.

How to get it?

CDK2-KO Tregs were previously reported to be functionally defective. Sequence analysis revealed cluster of 4 CDK motifs in N-terminal domain, 2 shown to be phosphorylated by CDK2/cyclin E complex.

Foxp3 with all 4 Ser/Thr residues mutated to alanine (S/T-->A) show increased protein half-life in cycloheximide-treated cells/amount of protein in cells, with no change in gene transcription.

S/T-->A Foxp3 transfected into naive Tcon  - induces stronger expression/repression of Foxp3 target genes than WT - exerts stronger suppression on Tcon proliferation - results in more complete recovery of colitis in Rag1KO mice transferred with Tcon

Hypothesised mechanism of destabilisation: CDK2 phosphorylation primes ubiquitination by E3 as a ‘phospho-degron’ - precedent in cyclin E.

Thymic Tregs repress expression of CDKs - to maintain Foxp3 stability? TGFb induces expression of p27kip1 which inhibits CDK2.

Fig 4

INTERESTING: Another example of phosphorylation affecting Foxp3 function. Does this mechanism have an adaptive role in Tregs in an active immune response, or is it more for the purposes of differentiation? Is CDK2 (or other CDKs) expression/activity triggered by immune activation or only cell cycle?

Tregs found in RA-synovial fluid (RA-SF) from patients in equal proportions compared to healthy SF and patient PBMC but are less suppressive in in vitro assays. - inhibition of suppressive capacity increases with increasing doses of RA-SF in culture. - effect replicated with TNFa alone but not other inflammatory cytokines found in RA-SF.

RA-SF Tregs express Foxp3 at similar level as normal Tregs but are less phosphorylated (by pSer/Tyr western) - phosphorylation is inhibited by RA-SF and TNFa.  - by site-directed mutagenesis, Ser418 identified as phosphorylation site required for full Treg activity.

TNFa signalling through NFkB upregulates PP1 phosphatase expression --> increased dephosphorylation of Ser418. - Ser418 is in C-terminal DNA-binding helix domain: phosphorylation may be required for adequate binding (adjacent lysine residues are acetylated). - Ser418 dephophorylation (or mutation to alanine S418A) increases IL-2 production, S418E (phosphoserine mimetic) decreases slightly compared to WT. 

Anti-TNFa therapy (infliximab) in human RA patients restores Foxp3 phosphorylation and suppressive function.

Fig 3

INTERESTING: Draws attention to the role of post-transcriptional modification in modulating Foxp3 function. What event/kinase drives Foxp3 phosphorylation upon activation? Are there other phosphorylation sites which modulate Treg suppression? NOTE: relevance for PI3K inhibition!