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

Curtis J. Pritzl, Dezzarae Luera, Karin M. Knudson, Michael J. Quaney, Michael J. Calcutt, Mark A. Daniels and Emma Teixeiro ()
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Curtis J. Pritzl: University of Missouri
Dezzarae Luera: University of Missouri
Karin M. Knudson: University of Missouri
Michael J. Quaney: University of Missouri
Michael J. Calcutt: University of Missouri
Mark A. Daniels: University of Missouri
Emma Teixeiro: University of Missouri

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40107-1

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