PXD018638-2

PXD018638 is an original dataset announced via ProteomeXchange.

Title	AIM2 in regulatory T (Treg) cells restrains autoimmune diseases
Description	The inflammasome initiates innate defense and inflammatory response by activating caspase-1 and pyroptotic cell death in myeloid cells1,2. It is comprised of an innate immune receptor/effector, pro-caspase-1 and a common adaptor molecule, ASC (apoptotic speck-containing protein with a CARD). Consistent with their pro-inflammatory function, inflammasome components including caspase-1, ASC and NLRP3, are known to exacerbate autoimmunity during experimental autoimmune encephalomyelitis (EAE) by enhancing IL-1 and IL-18 secretion in myeloid cells3-6. Here we show an unexpected function of a DNA-binding inflammasome effector, AIM2 (Absent in Melanoma 2)7-10, in restraining autoimmunity by performing EAE in both whole body and Treg-specific deletion of Aim2–/– mice. AIM2 is highly expressed by human and mouse Treg cells and it is essential to attenuate EAE. RNA-seq, biochemical and metabolic analyses revealed that AIM2 attenuates mTOR, Myc and immune-metabolic functions in both Treg cells isolated in vivo and Treg cells induced in vitro with TGF-. Importantly, we found AIM2 physically interacted with RACK1 in Treg cells to facility the PP2A/RACK1/Akt-mTOR signaling, which is identified as a central component downstream of AIM2 that controls Treg cell function and stability. While AIM2 is generally accepted as an inflammasome effector in myeloid cells, this report reveals a previously unappreciated T cell-intrinsic role of AIM2 in maintaining Treg cell function to restrain autoimmunity. This is achieved by diminishing Akt-mTOR signaling to regulate Treg stability under inflammation, and altering immune-metabolism in Treg cells.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:18:15.124.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ling Xie
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-18 15:31:35	ID requested
1	2021-01-26 22:44:29	announced
⏵ 2	2024-10-22 05:18:15	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: autoimmunity,AIM2 (Absent in Melanoma 2), Akt-mTOR signaling

Jenny P. -Y. Ting
contact affiliation	Department of Microbiology-Immunology, University of North Carolina at Chapel Hill, NC,
contact email	jenny_ting@med.unc.edu
lab head
Ling Xie
contact affiliation	UNC at Chapel Hill
contact email	xiel@email.unc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018638
     1. Label: PRIDE project
     2. Name: AIM2 in regulatory T (Treg) cells restrains autoimmune diseases