The interweaved signatures of common-gamma-chain cytokines across immunologic lineages

Alev Baysoy; Kumba Seddu; Tamara Salloum; Caleb A Dawson; Juliana J Lee; Liang Yang; Shani Gal-Oz; Hadas Ner-Gaon; Julie Tellier; Alberto Millan; Alexander Sasse; Brian Brown; Lewis L Lanier; Tal Shay; Stephen Nutt; Daniel Dwyer; Christophe Benoist; Immunological Genome Project Consortium

doi:10.1084/jem.20222052

The interweaved signatures of common-gamma-chain cytokines across immunologic lineages

J Exp Med. 2023 Jul 3;220(7):e20222052. doi: 10.1084/jem.20222052. Epub 2023 Mar 28.

Authors

Alev Baysoy^#^{1

2}, Kumba Seddu^#¹, Tamara Salloum³, Caleb A Dawson⁴, Juliana J Lee¹, Liang Yang¹, Shani Gal-Oz⁵, Hadas Ner-Gaon⁵, Julie Tellier⁴, Alberto Millan⁶, Alexander Sasse⁷, Brian Brown^{8

9}, Lewis L Lanier⁶, Tal Shay⁵, Stephen Nutt⁴, Daniel Dwyer³, Christophe Benoist^{1

2}; Immunological Genome Project Consortium

Affiliations

¹ Department of Immunology, Harvard Medical School , Boston, MA, USA.
² Broad Institute of MIT and Harvard , Cambridge, MA, USA.
³ Division of Allergy and Clinical Immunology, Brigham and Women's Hospital; and Department of Medicine, Harvard Medical School , Boston, MA, USA.
⁴ The Walter and Eliza Hall Institute of Medical Research and Department of Medical Biology, University of Melbourne , Parkville, Australia.
⁵ Department of Life Sciences, Ben-Gurion University of the Negev , Beer-Sheva, Israel.
⁶ Department of Microbiology and Immunology, University of California, San Francisco , San Francisco, CA, USA.
⁷ Paul G. Allen School of Computer Science and Engineering, University of Washington , Seattle, WA, USA.
⁸ Precision Immunology Institute, Icahn School of Medicine at Mount Sinai , New York, NY, USA.
⁹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai , New York, NY, USA.

^# Contributed equally.

Abstract

"γc" cytokines are a family whose receptors share a "common-gamma-chain" signaling moiety, and play central roles in differentiation, homeostasis, and communications of all immunocyte lineages. As a resource to better understand their range and specificity of action, we profiled by RNAseq the immediate-early responses to the main γc cytokines across all immunocyte lineages. The results reveal an unprecedented landscape: broader, with extensive overlap between cytokines (one cytokine doing in one cell what another does elsewhere) and essentially no effects unique to any one cytokine. Responses include a major downregulation component and a broad Myc-controlled resetting of biosynthetic and metabolic pathways. Various mechanisms appear involved: fast transcriptional activation, chromatin remodeling, and mRNA destabilization. Other surprises were uncovered: IL2 effects in mast cells, shifts between follicular and marginal zone B cells, paradoxical and cell-specific cross-talk between interferon and γc signatures, or an NKT-like program induced by IL21 in CD8+ T cells.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

CD8-Positive T-Lymphocytes*
Cell Differentiation
Cytokines*
Signal Transduction

Substances

Cytokines

Grants and funding

R24 AI072073/AI/NIAID NIH HHS/United States