Loading...
Thumbnail Image
Publication

A genetic screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation

Kiritsy, Michael C
Ankley, Laurisa M
Trombley, Justin
Huizinga, Gabrielle P
Lord, Audrey E
Orning, Pontus
Elling, Roland
Fitzgerald, Katherine A
Olive, Andrew J
Embargo Expiration Date
Abstract

Cytokine-mediated activation of host immunity is central to the control of pathogens. Interferon-gamma (IFNγ) is a key cytokine in protective immunity that induces major histocompatibility complex class II molecules (MHCII) to amplify CD4+ T cell activation and effector function. Despite its central role, the dynamic regulation of IFNγ-induced MHCII is not well understood. Using a genome-wide CRISPR-Cas9 screen in murine macrophages, we identified genes that control MHCII surface expression. Mechanistic studies uncovered two parallel pathways of IFNγ-mediated MHCII control that require the multifunctional glycogen synthase kinase three beta (GSK3β) or the mediator complex subunit 16 (MED16). Both pathways control distinct aspects of the IFNγ response and are necessary for IFNγ-mediated induction of the MHCII transactivator Ciita, MHCII expression, and CD4+ T cell activation. Our results define previously unappreciated regulation of MHCII expression that is required to control CD4+ T cell responses.

Source

Kiritsy MC, Ankley LM, Trombley J, Huizinga GP, Lord AE, Orning P, Elling R, Fitzgerald KA, Olive AJ. A genetic screen in macrophages identifies new regulators of IFNγ-inducible MHCII that contribute to T cell activation. Elife. 2021 Nov 8;10:e65110. doi: 10.7554/eLife.65110. PMID: 34747695; PMCID: PMC8598162.

Year of Medical School at Time of Visit
Sponsors
Dates of Travel
DOI
10.7554/eLife.65110
PubMed ID
34747695
Other Identifiers
Notes
Funding and Acknowledgements
Corresponding Author
Related Resources

This article is based on a previously available preprint in bioRxiv, https://doi.org/10.1101/2020.08.12.248252.

Related Resources
Repository Citation
Rights
Copyright Kiritsy et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.; Attribution 4.0 International