Zfp281 and Zfp148 control CD4+T cell thymic development and TH2 functions

Laura B. Chopp; Xiaoliang Zhu; Yayi Gao; Jia Nie; Jatinder Singh; Parimal Kumar; Kelly Z. Young; Shil Patel; Caiyi Li; Mariah Balmaceno-Cris; Melanie S. Vacchio; Michael M. Wang; Ferenc Livak; Juanita L. Merchant; Lie Wang; Michael C. Kelly; Jinfang Zhu; Rémy Bosselut

doi:10.1126/sciimmunol.adi9066

Zfp281 and Zfp148 control CD4⁺T cell thymic development and T_H2 functions

Laura B. Chopp, Xiaoliang Zhu, Yayi Gao, Jia Nie, Jatinder Singh, Parimal Kumar, Kelly Z. Young, Shil Patel, Caiyi Li, Mariah Balmaceno-Cris, Melanie S. Vacchio, Michael M. Wang, Ferenc Livak, Juanita L. Merchant, Lie Wang, Michael C. Kelly, Jinfang Zhu, Rémy Bosselut

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

How CD4+ lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by T helper cell type 2 (TH2) effector cells. Genetic, single-cell, and spatial transcriptomic analyses showed that these factors promote the intrathymic CD4+ T cell differentiation of class II major histocompatibility complex (MHC II)-restricted thymocytes, including expression of the CD4+ lineage-committing factor Thpok. In peripheral T cells, Zfp281 and Zfp148 promoted chromatin opening at and expression of TH2 cytokine genes but not of the TH2 lineage-determining transcription factor Gata3.We found that Zfp281 interacts with Gata3 and is recruited to Gata3 genomic binding sites at loci encoding Thpok and TH2 cytokines. Thus, Zfp148 and Zfp281 collaborate with Gata3 to promote CD4+ T cell development and TH2 cell responses.

Original language	English (US)
Article number	eadi9066
Journal	Science immunology
Volume	8
Issue number	89
DOIs	https://doi.org/10.1126/sciimmunol.adi9066
State	Published - 2023
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.1126/sciimmunol.adi9066

Cite this

Chopp, L. B., Zhu, X., Gao, Y., Nie, J., Singh, J., Kumar, P., Young, K. Z., Patel, S., Li, C., Balmaceno-Cris, M., Vacchio, M. S., Wang, M. M., Livak, F., Merchant, J. L., Wang, L., Kelly, M. C., Zhu, J., & Bosselut, R. (2023). Zfp281 and Zfp148 control CD4⁺T cell thymic development and T_H2 functions. Science immunology, 8(89), Article eadi9066. https://doi.org/10.1126/sciimmunol.adi9066

@article{62a65c35393c4c0588cf2a68ee5e1567,

title = "Zfp281 and Zfp148 control CD4+T cell thymic development and TH2 functions",

abstract = "How CD4+ lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by T helper cell type 2 (TH2) effector cells. Genetic, single-cell, and spatial transcriptomic analyses showed that these factors promote the intrathymic CD4+ T cell differentiation of class II major histocompatibility complex (MHC II)-restricted thymocytes, including expression of the CD4+ lineage-committing factor Thpok. In peripheral T cells, Zfp281 and Zfp148 promoted chromatin opening at and expression of TH2 cytokine genes but not of the TH2 lineage-determining transcription factor Gata3.We found that Zfp281 interacts with Gata3 and is recruited to Gata3 genomic binding sites at loci encoding Thpok and TH2 cytokines. Thus, Zfp148 and Zfp281 collaborate with Gata3 to promote CD4+ T cell development and TH2 cell responses.",

author = "Chopp, {Laura B.} and Xiaoliang Zhu and Yayi Gao and Jia Nie and Jatinder Singh and Parimal Kumar and Young, {Kelly Z.} and Shil Patel and Caiyi Li and Mariah Balmaceno-Cris and Vacchio, {Melanie S.} and Wang, {Michael M.} and Ferenc Livak and Merchant, {Juanita L.} and Lie Wang and Kelly, {Michael C.} and Jinfang Zhu and R{\'e}my Bosselut",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 The Authors.",

year = "2023",

doi = "10.1126/sciimmunol.adi9066",

language = "English (US)",

volume = "8",

journal = "Science immunology",

issn = "2470-9468",

publisher = "American Association for the Advancement of Science",

number = "89",

}

TY - JOUR

T1 - Zfp281 and Zfp148 control CD4+T cell thymic development and TH2 functions

AU - Chopp, Laura B.

AU - Zhu, Xiaoliang

AU - Gao, Yayi

AU - Nie, Jia

AU - Singh, Jatinder

AU - Kumar, Parimal

AU - Young, Kelly Z.

AU - Patel, Shil

AU - Li, Caiyi

AU - Balmaceno-Cris, Mariah

AU - Vacchio, Melanie S.

AU - Wang, Michael M.

AU - Livak, Ferenc

AU - Merchant, Juanita L.

AU - Wang, Lie

AU - Kelly, Michael C.

AU - Zhu, Jinfang

AU - Bosselut, Rémy

PY - 2023

Y1 - 2023

N2 - How CD4+ lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by T helper cell type 2 (TH2) effector cells. Genetic, single-cell, and spatial transcriptomic analyses showed that these factors promote the intrathymic CD4+ T cell differentiation of class II major histocompatibility complex (MHC II)-restricted thymocytes, including expression of the CD4+ lineage-committing factor Thpok. In peripheral T cells, Zfp281 and Zfp148 promoted chromatin opening at and expression of TH2 cytokine genes but not of the TH2 lineage-determining transcription factor Gata3.We found that Zfp281 interacts with Gata3 and is recruited to Gata3 genomic binding sites at loci encoding Thpok and TH2 cytokines. Thus, Zfp148 and Zfp281 collaborate with Gata3 to promote CD4+ T cell development and TH2 cell responses.

AB - How CD4+ lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by T helper cell type 2 (TH2) effector cells. Genetic, single-cell, and spatial transcriptomic analyses showed that these factors promote the intrathymic CD4+ T cell differentiation of class II major histocompatibility complex (MHC II)-restricted thymocytes, including expression of the CD4+ lineage-committing factor Thpok. In peripheral T cells, Zfp281 and Zfp148 promoted chromatin opening at and expression of TH2 cytokine genes but not of the TH2 lineage-determining transcription factor Gata3.We found that Zfp281 interacts with Gata3 and is recruited to Gata3 genomic binding sites at loci encoding Thpok and TH2 cytokines. Thus, Zfp148 and Zfp281 collaborate with Gata3 to promote CD4+ T cell development and TH2 cell responses.

UR - http://www.scopus.com/inward/record.url?scp=85176463346&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85176463346&partnerID=8YFLogxK

U2 - 10.1126/sciimmunol.adi9066

DO - 10.1126/sciimmunol.adi9066

M3 - Article

C2 - 37948511

SN - 2470-9468

VL - 8

JO - Science immunology

JF - Science immunology

IS - 89

M1 - eadi9066

ER -

Zfp281 and Zfp148 control CD4⁺T cell thymic development and T_H2 functions

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this