The Inflammasome Adaptor ASC Intrinsically Limits CD4+ T-Cell Proliferation to Help Maintain Intestinal Homeostasis

Frontiers in Immunology
Hanif Javanmard KhamenehAlessandra Mortellaro

Abstract

The inflammasome is a multi-protein complex that mediates proteolytic cleavage and release of the pro-inflammatory cytokines IL-1β and IL-18, and pyroptosis-a form of cell death induced by various pathogenic bacteria. Apoptosis-associated speck-like protein containing a CARD (ASC) has a pivotal role in inflammasome assembly and activation. While ASC function has been primarily implicated in innate immune cells, its contribution to lymphocyte biology is unclear. Here we report that ASC is constitutively expressed in naïve CD4+ T cells together with the inflammasome sensor NLRP3 and caspase-1. When adoptively transferred in immunocompromised Rag1-/- mice, Asc-/- CD4+ T cells exacerbate T-cell-mediated autoimmune colitis. Asc-/- CD4+ T cells exhibit a higher proliferative capacity in vitro than wild-type CD4+ T cells. The increased expansion of Asc-/- CD4+ T cells in vivo correlated with robust TCR-mediated activation, inflammatory activity, and higher metabolic profile toward a highly glycolytic phenotype. These findings identify ASC as a crucial intrinsic regulator of CD4+ T-cell expansion that serves to maintain intestinal homeostasis.

References

Apr 1, 1996·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·L G AxelssonA C Bylund-Fellenius
Nov 24, 1999·The Journal of Biological Chemistry·J MasumotoJ Sagara
Feb 13, 2001·Biochemical and Biophysical Research Communications·J MasumotoJ Sagara
Sep 19, 2001·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·J MasumotoJ Sagara
Dec 18, 2002·The Journal of Experimental Medicine·Christian StehlikJohn C Reed
May 31, 2003·Oncogene·Jeoffrey J LevinePaula M Vertino
Jun 11, 2004·Nature·Sanjeev MariathasanVishva M Dixit
Oct 7, 2004·The American Journal of Pathology·Annalisa R StonePaula M Vertino
Jul 20, 2006·Molecular Cancer·Partha M DasRakesh Singal
Mar 14, 2007·Molecular Cell·Benjamin FaustinJohn C Reed
Feb 19, 2009·Cancer Research·Melissa J ParsonsPaula M Vertino
Apr 7, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Patrick J ShawThirumala-Devi Kanneganti
Nov 8, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cristina Conforti-AndreoniAlessandra Mortellaro
Oct 16, 2012·The Journal of Biological Chemistry·Parimala R VajjhalaJustine M Hill
Nov 30, 2013·Cellular and Molecular Life Sciences : CMLS·Antero SalminenKai Kaarniranta
Jan 5, 2014·Nature Protocols·Simone PicelliRickard Sandberg
Apr 18, 2014·The Journal of Pathology·Lia Paola Zambetti, Alessandra Mortellaro
Jun 23, 2015·Nature Immunology·Mélanie BruchardFrançois Ghiringhelli
Jun 14, 2016·Nature Reviews. Immunology·Petr Broz, Vishva M Dixit
Jun 29, 2016·Cancer Medicine·Nagisa OkadaShigeaki Hida
Sep 28, 2016·Trends in Biochemical Sciences·Yuan HeGabriel Núñez
Oct 21, 2016·Cellular and Molecular Life Sciences : CMLS·Florian HossEicke Latz
Jan 11, 2017·Gastroenterology Research and Practice·Francesca A R SilvaRaquel F Leal
Apr 13, 2017·Mucosal Immunology·N ZmoraE Elinav
Nov 10, 2017·International Journal of Molecular Sciences·Nicole RansonRajaraman Eri

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Citations

Oct 3, 2021·Journal of Molecular Biology·Andreas Linder, Veit Hornung

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Datasets Mentioned

BETA
GSE120928

Methods Mentioned

BETA
ELISA
PMA
flow cytometry
Antibody Array
FACS
electrophoresis

Software Mentioned

ComplexHeatmap
GraphPad
R
GraphPad Prism
Bioconductor
Pycard
topGO
Bioconductor package
edgeR

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis