tetano
Editor, Senior Moderator
Nat Commun
. 2023 Mar 24;14(1):1652.
doi: 10.1038/s41467-023-37420-0.
Aiolos represses CD4[SUP]+[/SUP] T cell cytotoxic programming via reciprocal regulation of T[SUB]FH[/SUB] transcription factors and IL-2 sensitivity
Kaitlin A Read[SUP] #[/SUP][SUP] 1 2 [/SUP], Devin M Jones[SUP] #[/SUP][SUP] 1 2 [/SUP], Srijana Pokhrel[SUP] 1 [/SUP], Emily D S Hales[SUP] 1 [/SUP], Aditi Varkey[SUP] 1 [/SUP], Jasmine A Tuazon[SUP] 1 2 3 [/SUP], Caprice D Eisele[SUP] 2 4 [/SUP], Omar Abdouni[SUP] 1 [/SUP], Abbey Saadey[SUP] 1 2 [/SUP], Melissa R Leonard[SUP] 1 5 [/SUP], Robert T Warren[SUP] 1 [/SUP], Michael D Powell[SUP] 6 [/SUP], Jeremy M Boss[SUP] 6 [/SUP], Emily A Hemann[SUP] 1 7 [/SUP], Jacob S Yount[SUP] 1 7 [/SUP], Gang Xin[SUP] 1 8 [/SUP], Hazem E Ghoneim[SUP] 1 8 [/SUP], Chan-Wang J Lio[SUP] 1 8 [/SUP], Aharon G Freud[SUP] 4 8 [/SUP], Patrick L Collins[SUP] 1 8 [/SUP], Kenneth J Oestreich[SUP] 9 10 11 [/SUP]
Affiliations
Abstract
During intracellular infection, T follicular helper (T[SUB]FH[/SUB]) and T helper 1 (T[SUB]H[/SUB]1) cells promote humoral and cell-mediated responses, respectively. Another subset, CD4-cytotoxic T lymphocytes (CD4-CTLs), eliminate infected cells via functions typically associated with CD8[SUP]+[/SUP] T cells. The mechanisms underlying differentiation of these populations are incompletely understood. Here, we identify the transcription factor Aiolos as a reciprocal regulator of T[SUB]FH[/SUB] and CD4-CTL programming. We find that Aiolos deficiency results in downregulation of key T[SUB]FH[/SUB] transcription factors, and consequently reduced T[SUB]FH[/SUB] differentiation and antibody production, during influenza virus infection. Conversely, CD4-CTL programming is elevated, including enhanced Eomes and cytolytic molecule expression. We further demonstrate that Aiolos deficiency allows for enhanced IL-2 sensitivity and increased STAT5 association with CD4-CTL gene targets, including Eomes, effector molecules, and IL2Ra. Thus, our collective findings identify Aiolos as a pivotal regulator of CD4-CTL and T[SUB]FH[/SUB] programming and highlight its potential as a target for manipulating CD4[SUP]+[/SUP] T cell responses.
. 2023 Mar 24;14(1):1652.
doi: 10.1038/s41467-023-37420-0.
Aiolos represses CD4[SUP]+[/SUP] T cell cytotoxic programming via reciprocal regulation of T[SUB]FH[/SUB] transcription factors and IL-2 sensitivity
Kaitlin A Read[SUP] #[/SUP][SUP] 1 2 [/SUP], Devin M Jones[SUP] #[/SUP][SUP] 1 2 [/SUP], Srijana Pokhrel[SUP] 1 [/SUP], Emily D S Hales[SUP] 1 [/SUP], Aditi Varkey[SUP] 1 [/SUP], Jasmine A Tuazon[SUP] 1 2 3 [/SUP], Caprice D Eisele[SUP] 2 4 [/SUP], Omar Abdouni[SUP] 1 [/SUP], Abbey Saadey[SUP] 1 2 [/SUP], Melissa R Leonard[SUP] 1 5 [/SUP], Robert T Warren[SUP] 1 [/SUP], Michael D Powell[SUP] 6 [/SUP], Jeremy M Boss[SUP] 6 [/SUP], Emily A Hemann[SUP] 1 7 [/SUP], Jacob S Yount[SUP] 1 7 [/SUP], Gang Xin[SUP] 1 8 [/SUP], Hazem E Ghoneim[SUP] 1 8 [/SUP], Chan-Wang J Lio[SUP] 1 8 [/SUP], Aharon G Freud[SUP] 4 8 [/SUP], Patrick L Collins[SUP] 1 8 [/SUP], Kenneth J Oestreich[SUP] 9 10 11 [/SUP]
Affiliations
- PMID: 36964178
- PMCID: PMC10039023
- DOI: 10.1038/s41467-023-37420-0
Abstract
During intracellular infection, T follicular helper (T[SUB]FH[/SUB]) and T helper 1 (T[SUB]H[/SUB]1) cells promote humoral and cell-mediated responses, respectively. Another subset, CD4-cytotoxic T lymphocytes (CD4-CTLs), eliminate infected cells via functions typically associated with CD8[SUP]+[/SUP] T cells. The mechanisms underlying differentiation of these populations are incompletely understood. Here, we identify the transcription factor Aiolos as a reciprocal regulator of T[SUB]FH[/SUB] and CD4-CTL programming. We find that Aiolos deficiency results in downregulation of key T[SUB]FH[/SUB] transcription factors, and consequently reduced T[SUB]FH[/SUB] differentiation and antibody production, during influenza virus infection. Conversely, CD4-CTL programming is elevated, including enhanced Eomes and cytolytic molecule expression. We further demonstrate that Aiolos deficiency allows for enhanced IL-2 sensitivity and increased STAT5 association with CD4-CTL gene targets, including Eomes, effector molecules, and IL2Ra. Thus, our collective findings identify Aiolos as a pivotal regulator of CD4-CTL and T[SUB]FH[/SUB] programming and highlight its potential as a target for manipulating CD4[SUP]+[/SUP] T cell responses.