Saturday, February 10, 2018

CD4 T cells silence innate over-activation to gut microbiota

A simple but very effective study was published in journal Nature from Ron Germain's lab. His group is known for publishing high quality in situ microscopy data combined with cellular analysis. New study continues this trend. 

In this study the authors analyzed pattern of phosphorylation of STAT3 transcription factor in small intestine derived from various immune deficient mouse strains. Compared to WT mice, pSTAT3 staining in RAG1 KO gut tissue (lacking adaptive immune system) was significantly up-regulated. 



Analysis of antibiotic-treated or germ-free mice indicated that pattern of pSTAT3 staining in RAG1-KO was correlated with the presence of gut microbiota.




Interestingly, longitudinal analysis showed that pSTAT3 staining inversely correlated with  maturation of adaptive immune system post weaning (between 4-20 weeks). 



Co-housing experiments showed that T cells, but not B cells, played a role in silencing innate pSTAT3 over-activation.



And out of T cells, it were CD4 T cells and class II antigen-presentation that played the role in pSTAT3 silencing.



Finally, both Tregs and SBF-specific Th17 cells (7B8 transgenic T cells) could mediate silencing of pSTAT3 over-activation. Both T cell type could down-regulate STAT3 phosphorylation in innate and epithelial cells but the mechanisms could be different. 




In summary, this study showed that persistent pSTAT3 over-activation observed in mice deficient for CD4 T cell function could explain some of chronic metabolic shifts observed in clinical settings. 

posted by David Usharauli


3 comments:

  1. For me it is not clear why b2m-/- H2-ab1-/- mice show pSTAT3 staining? Do they have explanation in article?
    P.s. really nice study BTW.

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  2. I think it is because b2m-/- H2-ab1-/- double knockout mice lack CD4 T cells necessary to silence pSTAT3. Isn't correct?

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  3. o, yes. effect mediated through H2-ab1-/-. I got it

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