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Comment
. 2021 Mar 9;54(3):397-398.
doi: 10.1016/j.immuni.2021.02.005.

Essential functions of regulatory T cell TGF-β1 revealed by differential gene-targeting approaches

Emmanuel Stephen-Victor  1 , Ye Cui  1 , Ziwei Wang  2 , Mehdi Benamar  1 , Louis-Marie Charbonnier  1 , Talal A Chatila  3
Affiliations
Comment

Essential functions of regulatory T cell TGF-β1 revealed by differential gene-targeting approaches

Emmanuel Stephen-Victor et al. Immunity. .
No abstract available

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Conflict of interest statement

Declaration of interests T.A.C. is an inventor on published US patent no. US10391131B2, submitted by The Brigham and Women’s Hospital, Inc. and Children’s Medical Center Corporation, which covers methods and compositions for prevention and treatment of food allergy using microbial treatments. T.A.C. and E.S.-V. have pending patent applications related to the use of probiotics in enforcing oral tolerance in food allergy (no. 62/798,224). T.A.C. is a co-founder and has equity in Paretobio.

Figures

Figure 1.
Figure 1.. Differential impact of Tgfb1 exon 6 versus exon 3 deletion in Treg cells.
(A). Schematic presentation of the floxed Tgfb1 exon 6 locus, detailing the proximal and distal Loxp sequences and the positions of the primers used in Sanger sequencing studies. Primers P1 and P2 were used to sequence the entire locus, P3 and P4 for the proximal and P5 and P6 for the distal loxp sites. (B). Gel electrophoresis analysis of P1 and P2 PCR amplicons obtained using genomic DNA of Foxp3YFPCreTgfb1Ex6Δ/Δ and Foxp3YFPCre Treg cells. Long arrow indicates the position of 350bp post Cre excision PCR product, while the short arrow indicates the position of the unexcised full length sequence. (C). Sanger sequencing of the 350bp Cre excision PCR product shown in panel B detailing the position of introns 5 and 6 and the post excision retained Loxp sequence. (D). Representative flow cytometric plots, frequencies and numbers of Treg cells in peripheral lymph nodes (PLN) (D), mesenteric lymph nodes (MLN) (E), Spleen (F), and Blood (G) from Foxp3YFPCre, Foxp3YFPCreTgfb1Ex6Δ/+, and Foxp3YFPCreTgfb1Ex6Δ/Δ mice. (H). Representative flow cytometric plots and frequencies of Annexin V+ Treg cells from the spleens of the respective mouse strains. (I). Real time PCR analysis of relative mRNA expression of Ffar2, Il4ra, Relb, and Irf7 in Foxp3YFPCre and Foxp3YFPCreTgfb1Ex6Δ/Δ Treg cells. (J). ELISA Quantification of TGFβ1 production by anti-CD3+anti-CD28 mAb +IL-2-activated Treg cells isolated from Foxp3YFPCre and Foxp3YFPCreTgfb1Ex6Δ/Δ mice (BALB/c background) and Foxp3YFPCre and Foxp3YFPCreTgfb1Ex3Δ/Δ mice (C57BL/6 background). (K). Immunoblot analysis of TGFβ1 in cell lysate of Treg cells from Foxp3YFPCre and Foxp3YFPCreTgfb1Ex6Δ/Δ (BLAB/c) and Foxp3YFPCre and Foxp3YFPCreTgfb1Ex3Δ/Δ (C57Bl/6) mice. Representative immunoblot, densitometric analysis of latent TGFβ1 and mature TGFβ1 expression in Treg cells. (L). Core body temperature drop following OVA challenge of OVA-SEB sensitized Foxp3YFPCre and Foxp3YFPCreTgfb1Ex3Δ/Δ mice. (M) Serum concentrations of IgE at baseline and post Ova challenge; OVA-specific IgE and MMCP-1 (N-P). Flow cytometric analysis and enumeration of c-Kit+FcεRI+IgE+ mast cells, RORγt+ and GATA3+ Treg cells and IL-4+ Treg and Teff cells (P) in the in the small intestines (SI) of the mouse groups in (L). Results are representative of at least 3 independent experiments. Each symbol represents an independent sample. Numbers in flow plots indicate percentages. Error bars indicate SEM. Statistical tests: Two-way ANOVA (L); One-way ANOVA (D, E, G, H) Student’s t-test (I to K; and M to Q). *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.
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References

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