tetano
Editor, Senior Moderator
Mucosal Immunol. 2019 May 15. doi: 10.1038/s41385-019-0173-1. [Epub ahead of print]
[h=1]IRF4-dependent dendritic cells regulate CD8[SUP]+[/SUP] T-cell differentiation and memory responses in influenza infection.[/h] Ainsua-Enrich E[SUP]1[/SUP], Hatipoglu I[SUP]1[/SUP], Kadel S[SUP]1,[/SUP][SUP]2[/SUP], Turner S[SUP]1[/SUP], Paul J[SUP]1[/SUP], Singh S[SUP]1[/SUP], Bagavant H[SUP]1[/SUP], Kovats S[SUP]3,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Acute respiratory disease caused by influenza viruses is imperfectly mitigated by annual vaccination to select strains. Development of vaccines that elicit lung-resident memory CD8[SUP]+[/SUP] T cells (T[SUB]RM[/SUB]) would offer more universal protection to seasonal and emerging pandemic viruses. Understanding how lung-resident dendritic cells (DCs) regulate T[SUB]RM[/SUB] differentiation would be an important step in this process. Here, we used CD11c-cre-Irf4[SUP]f/f[/SUP] (KO) mice, which lack lung-resident IRF4-dependent CD11b[SUP]+[/SUP]CD24[SUP]hi[/SUP] DCs and show IRF4 deficiency in other lung cDC subsets, to determine if IRF4-expressing DCs regulate CD8[SUP]+[/SUP] memory precursor cells and T[SUB]RM[/SUB] during influenza A virus (IAV) infection. KO mice showed defective CD8[SUP]+[/SUP] T-cell memory, stemming from a deficit of T regulatory cells and memory precursor cells with decreased Foxo1 expression. Transfer of wild-type CD11b[SUP]+[/SUP]CD24[SUP]hi[/SUP] DCs into KO mice restored CD8[SUP]+[/SUP] memory precursor cell numbers to wild-type levels. KO mice recovered from a primary infection harbored reduced numbers of CD8[SUP]+[/SUP] T[SUB]RM[/SUB] and showed deficient expansion of IFNγ[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells and increased lung pathology upon challenge with heterosubtypic IAV. Thus, vaccination strategies that harness the function of IRF4-dependent DCs could promote the differentiation of CD8[SUP]+[/SUP] T[SUB]RM[/SUB] during IAV infection.
PMID: 31089186 PMCID: PMC6527354 [Available on 2019-11-15] DOI: 10.1038/s41385-019-0173-1
[h=1]IRF4-dependent dendritic cells regulate CD8[SUP]+[/SUP] T-cell differentiation and memory responses in influenza infection.[/h] Ainsua-Enrich E[SUP]1[/SUP], Hatipoglu I[SUP]1[/SUP], Kadel S[SUP]1,[/SUP][SUP]2[/SUP], Turner S[SUP]1[/SUP], Paul J[SUP]1[/SUP], Singh S[SUP]1[/SUP], Bagavant H[SUP]1[/SUP], Kovats S[SUP]3,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Acute respiratory disease caused by influenza viruses is imperfectly mitigated by annual vaccination to select strains. Development of vaccines that elicit lung-resident memory CD8[SUP]+[/SUP] T cells (T[SUB]RM[/SUB]) would offer more universal protection to seasonal and emerging pandemic viruses. Understanding how lung-resident dendritic cells (DCs) regulate T[SUB]RM[/SUB] differentiation would be an important step in this process. Here, we used CD11c-cre-Irf4[SUP]f/f[/SUP] (KO) mice, which lack lung-resident IRF4-dependent CD11b[SUP]+[/SUP]CD24[SUP]hi[/SUP] DCs and show IRF4 deficiency in other lung cDC subsets, to determine if IRF4-expressing DCs regulate CD8[SUP]+[/SUP] memory precursor cells and T[SUB]RM[/SUB] during influenza A virus (IAV) infection. KO mice showed defective CD8[SUP]+[/SUP] T-cell memory, stemming from a deficit of T regulatory cells and memory precursor cells with decreased Foxo1 expression. Transfer of wild-type CD11b[SUP]+[/SUP]CD24[SUP]hi[/SUP] DCs into KO mice restored CD8[SUP]+[/SUP] memory precursor cell numbers to wild-type levels. KO mice recovered from a primary infection harbored reduced numbers of CD8[SUP]+[/SUP] T[SUB]RM[/SUB] and showed deficient expansion of IFNγ[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells and increased lung pathology upon challenge with heterosubtypic IAV. Thus, vaccination strategies that harness the function of IRF4-dependent DCs could promote the differentiation of CD8[SUP]+[/SUP] T[SUB]RM[/SUB] during IAV infection.
PMID: 31089186 PMCID: PMC6527354 [Available on 2019-11-15] DOI: 10.1038/s41385-019-0173-1