Identification of Casz1 as a Regulatory Protein Controlling T Helper Cell Differentiation, Inflammation, and Immunity

Frontiers in Immunology
Natarajan BhaskaranPushpa Pandiyan

Abstract

While T helper (Th) cells play a crucial role in host defense, an imbalance in Th effector subsets due to dysregulation in their differentiation and expansion contribute to inflammatory disorders. Here, we show that Casz1, whose function is previously unknown in CD4+ T cells, coordinates Th differentiation in vitro and in vivo. Casz1 deficiency in CD4+ T cells lowers susceptibility to experimental autoimmune encephalomyelitis, consistent with the reduced frequency of Th17 cells, despite an increase in Th1 cells in mice. Loss of Casz1 in the context of mucosal Candida infection severely impairs Th17 and Treg responses, and lowers the ability of the mice to clear the secondary infection. Importantly, in both the models, absence of Casz1 causes a significant diminution in IFN-γ+IL-17A+ double-positive inflammatory Th17 cells (Th1* cells) in tissues in vivo. Transcriptome analyses of CD4+ T cells lacking Casz1 show a signature consistent with defective Th17 differentiation. With regards to Th17 differentiation, Casz1 limits repressive histone marks and enables acquisition of permissive histone marks at Rorc, Il17a, Ahr, and Runx1 loci. Taken together, these data identify Casz1 as a new Th plasticity regulator having important clini...Continue Reading

References

Oct 16, 2001·Antimicrobial Agents and Chemotherapy·Y KamaiS G Filler
Mar 4, 2003·Nature Reviews. Cancer·Garrett M Brodeur
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jan 5, 2007·Annual Review of Immunology·Casey T WeaverLaurie E Harrington
May 9, 2007·Nature Immunology·Eva V Acosta-RodriguezGiorgio Napolitani
Jun 2, 2007·Journal of Periodontology·Jill M Kramer, Sarah L Gaffen
Jan 29, 2008·Seminars in Immunology·J S StumhoferC A Hunter
Apr 16, 2008·Developmental Cell·Kathleen S Christine, Frank L Conlon
Dec 17, 2008·Annals of the New York Academy of Sciences·Gustavo J MartinezChen Dong
Jan 2, 2009·Advances in Immunology·Darrell B O'QuinnCasey T Weaver
Jan 10, 2009·Annual Review of Immunology·Thomas KornVijay K Kuchroo
Feb 11, 2009·The Journal of Experimental Medicine·Heather R ContiSarah L Gaffen
Mar 6, 2009·International Immunology·Amit Awasthi, Vijay K Kuchroo
Mar 31, 2009·Current Opinion in Immunology·Liang Zhou, Dan R Littman
Nov 19, 2010·Cytokine & Growth Factor Reviews·Kiyoshi HiraharaJohn J O'Shea
Dec 16, 2010·Annals of the New York Academy of Sciences·Yan HuWenjun Ouyang
Jan 29, 2011·Experimental & Molecular Medicine·Chen Dong
Mar 26, 2011·Nature Reviews. Immunology·John J O'SheaYuka Kanno
Nov 29, 2011·Nature·Michael D RosenblumAbul K Abbas
Apr 3, 2012·Nature·Christina E ZielinskiFederica Sallusto
Jul 4, 2012·Nature Immunology·Francisco J QuintanaVijay K Kuchroo
Sep 21, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pushpa PandiyanMichael J Lenardo
Oct 2, 2012·Cell·Maria CiofaniDan R Littman
Nov 23, 2012·Cancer Research·Kai-Oliver HenrichFrank Westermann
Dec 20, 2012·Mucosal Immunology·N Hernández-SantosS L Gaffen
Jan 18, 2013·Blood·Pawel Muranski, Nicholas P Restifo
Apr 2, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rebekka DuhenEstelle Bettelli
Dec 1, 2011·Therapeutic Advances in Hematology·Kara L Davis
Feb 11, 2014·The Journal of Clinical Investigation·Robert Sanchez RodriguezMichael D Rosenblum
Dec 20, 2015·Immunity·Dhavalkumar D Patel, Vijay K Kuchroo

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Citations

Mar 25, 2019·Frontiers in Immunology·Pushpa PandiyanJochen Huehn
May 1, 2021·Genes·Marco MilanesiPaolo Ajmone-Marsan

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Methods Mentioned

BETA
enzyme linked immunosorbent assay
PCR
RNA-seq
Immunoprecipitation
PMA
fluorescence-activated cell sorting
fluorescence-activated
flow cytometry
ChIP
acetylation

Software Mentioned

Excel
R
Ensembl
GSEA
Trimmomatic
STAR
Prism
GENCODE
FlowJo
R Package limma

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