tetano
Editor, Senior Moderator
Nat Commun
. 2023 Jul 19;14(1):4331.
doi: 10.1038/s41467-023-40107-1. IKK2/NFkB signaling controls lung resident CD8[SUP]+[/SUP] T cell memory during influenza infection
Curtis J Pritzl[SUP] 1 2 [/SUP], Dezzarae Luera[SUP] 1 2 [/SUP], Karin M Knudson[SUP] 1 [/SUP], Michael J Quaney[SUP] 1 [/SUP], Michael J Calcutt[SUP] 3 [/SUP], Mark A Daniels[SUP] 1 2 [/SUP], Emma Teixeiro[SUP] 4 5 [/SUP]
Affiliations
CD8[SUP]+[/SUP] T cell tissue resident memory (T[SUB]RM[/SUB]) 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[SUP]+[/SUP] T[SUB]RM[/SUB] maintenance. By contrast, enhancing NFkB signals during the contraction phase of the response leads to a defect in CD8[SUP]+[/SUP] T[SUB]RM[/SUB] 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[SUP]+[/SUP] T[SUB]RM[/SUB] imprinting molecules CD69, CD103, Runx3 and Eomes. Conversely, inhibiting NFkB signals not only recovers but improves the transcriptional signature and generation of lung CD8[SUP]+[/SUP] T[SUB]RM[/SUB]. 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[SUP]+[/SUP] T[SUB]RM[/SUB].
. 2023 Jul 19;14(1):4331.
doi: 10.1038/s41467-023-40107-1. IKK2/NFkB signaling controls lung resident CD8[SUP]+[/SUP] T cell memory during influenza infection
Curtis J Pritzl[SUP] 1 2 [/SUP], Dezzarae Luera[SUP] 1 2 [/SUP], Karin M Knudson[SUP] 1 [/SUP], Michael J Quaney[SUP] 1 [/SUP], Michael J Calcutt[SUP] 3 [/SUP], Mark A Daniels[SUP] 1 2 [/SUP], Emma Teixeiro[SUP] 4 5 [/SUP]
Affiliations
- PMID: 37468506
- PMCID: PMC10356942
- DOI: 10.1038/s41467-023-40107-1
CD8[SUP]+[/SUP] T cell tissue resident memory (T[SUB]RM[/SUB]) 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[SUP]+[/SUP] T[SUB]RM[/SUB] maintenance. By contrast, enhancing NFkB signals during the contraction phase of the response leads to a defect in CD8[SUP]+[/SUP] T[SUB]RM[/SUB] 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[SUP]+[/SUP] T[SUB]RM[/SUB] imprinting molecules CD69, CD103, Runx3 and Eomes. Conversely, inhibiting NFkB signals not only recovers but improves the transcriptional signature and generation of lung CD8[SUP]+[/SUP] T[SUB]RM[/SUB]. 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[SUP]+[/SUP] T[SUB]RM[/SUB].