A Caltech Library Service

Aging-associated HELIOS deficiency in naive CD4⁺ T cells alters chromatin remodeling and promotes effector cell responses

Zhang, Huimin and Jadhav, Rohit R. and Cao, Wenqiang and Goronzy, Isabel N. and Zhao, Tuantuan V. and Jin, Jun and Ohtsuki, Shozo and Hu, Zhaolan and Morales, Jose and Greenleaf, William J. and Weyand, Cornelia M. and Goronzy, Jörg J. (2023) Aging-associated HELIOS deficiency in naive CD4⁺ T cells alters chromatin remodeling and promotes effector cell responses. Nature Immunology, 24 (1). pp. 96-109. ISSN 1529-2908. doi:10.1038/s41590-022-01369-x.

Full text is not posted in this repository. Consult Related URLs below.

Use this Persistent URL to link to this item:


Immune aging combines cellular defects in adaptive immunity with the activation of pathways causing a low-inflammatory state. Here we examined the influence of age on the kinetic changes in the epigenomic and transcriptional landscape induced by T cell receptor (TCR) stimulation in naive CD4⁺ T cells. Despite attenuated TCR signaling in older adults, TCR activation accelerated remodeling of the epigenome and induced transcription factor networks favoring effector cell differentiation. We identified increased phosphorylation of STAT5, at least in part due to aberrant IL-2 receptor and lower HELIOS expression, as upstream regulators. Human HELIOS-deficient, naive CD4⁺ T cells, when transferred into human-synovium-mouse chimeras, infiltrated tissues more efficiently. Inhibition of IL-2 or STAT5 activity in T cell responses of older adults restored the epigenetic response pattern to the one seen in young adults. In summary, reduced HELIOS expression in non-regulatory naive CD4⁺ T cells in older adults directs T cell fate decisions toward inflammatory effector cells that infiltrate tissue.

Item Type:Article
Related URLs:
URLURL TypeDescription ReadCube access
Zhang, Huimin0000-0003-1143-9388
Jadhav, Rohit R.0000-0002-2999-6329
Cao, Wenqiang0000-0002-5024-0817
Goronzy, Isabel N.0000-0002-6713-9192
Zhao, Tuantuan V.0000-0002-8365-2738
Jin, Jun0000-0002-5018-144X
Ohtsuki, Shozo0000-0001-8954-5709
Hu, Zhaolan0000-0003-1137-0579
Greenleaf, William J.0000-0003-1409-3095
Weyand, Cornelia M.0000-0003-2230-9802
Goronzy, Jörg J.0000-0001-7670-1856
Additional Information:This work was supported by the National Institutes of Health (R01 AR042527, R01 HL117913, R01 AI108906, R01 HL142068 and P01 HL129941 to C.M.W. and R01 AI108891, R01 AG045779, U19 AI057266 and R01 AI129191 to J.J.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank E. Fischer from Harvard Medical School for providing the ALV2 compound, P. Li from the National Institutes of Health for providing processed ChIP-seq data files of human CD4⁺ T cells, C. Gustafson and F. Müller for suggestions on single-cell data analysis, X. Wang and F. Cao for suggestions on ATAC-seq time course analysis and the Stanford Genome Sequencing Service Center and Novogen for providing sequencing services. Contributions. H.Z., R.R.J., W.J.G., C.M.W. and J.J.G. designed the research and interpreted data. H.Z., W.C., T.Z., J.J., S.O., J.M. and Z.H. performed experimental work. R.R.J. and I.N.G. analyzed high-throughput data. H.Z., R.R.J. and J.J.G. wrote the manuscript. Data availability. Raw sequencing data have been deposited in SRA with the BioProject accession no. PRJNA757466. Raw experimental data will be provided by the corresponding author upon request. Source data are provided with this paper. Competing interests. W.J.G. has affiliations with 10x Genomics (consultant). The other authors declare no competing interests.
Funding AgencyGrant Number
NIHR01 AR042527
NIHR01 HL117913
NIHR01 AI108906
NIHR01 HL142068
NIHP01 HL129941
NIHR01 AI108891
NIHR01 AG045779
NIHU19 AI057266
NIHR01 AI129191
Issue or Number:1
Record Number:CaltechAUTHORS:20230215-681031000.1
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:119288
Deposited By: George Porter
Deposited On:15 Feb 2023 18:57
Last Modified:15 Feb 2023 18:57

Repository Staff Only: item control page