IKK2/NFkB signaling controls lung resident CD8+ T cell memory during influenza infection

Bibliographic Details
Title: IKK2/NFkB signaling controls lung resident CD8+ T cell memory during influenza infection
Authors: Curtis J. Pritzl, Dezzarae Luera, Karin M. Knudson, Michael J. Quaney, Michael J. Calcutt, Mark A. Daniels, Emma Teixeiro
Source: Nature Communications, Vol 14, Iss 1, Pp 1-14 (2023)
Publisher Information: Nature Portfolio, 2023.
Publication Year: 2023
Collection: LCC:Science
Subject Terms: Science
More Details: Abstract CD8+ T cell tissue resident memory (TRM) cells are especially suited to control pathogen spread at mucosal sites. However, their maintenance in lung is short-lived. TCR-dependent NFkB signaling is crucial for T cell memory but how and when NFkB signaling modulates tissue resident and circulating T cell memory during the immune response is unknown. Here, we find that enhancing NFkB signaling in T cells once memory to influenza is established, increases pro-survival Bcl-2 and CD122 levels thus boosting lung CD8+ TRM maintenance. By contrast, enhancing NFkB signals during the contraction phase of the response leads to a defect in CD8+ TRM differentiation without impairing recirculating memory subsets. Specifically, inducible activation of NFkB via constitutive active IKK2 or TNF interferes with TGFβ signaling, resulting in defects of lung CD8+ TRM imprinting molecules CD69, CD103, Runx3 and Eomes. Conversely, inhibiting NFkB signals not only recovers but improves the transcriptional signature and generation of lung CD8+ TRM. Thus, NFkB signaling is a critical regulator of tissue resident memory, whose levels can be tuned at specific times during infection to boost lung CD8+ TRM.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-023-40107-1
Access URL: https://doaj.org/article/8618125c2d3f4f26b08eaa38d8d3c4c7
Accession Number: edsdoj.8618125c2d3f4f26b08eaa38d8d3c4c7
Database: Directory of Open Access Journals
More Details
ISSN:20411723
DOI:10.1038/s41467-023-40107-1
Published in:Nature Communications
Language:English