tetano
Editor, Senior Moderator
Nat Immunol
. 2023 Nov 9.
doi: 10.1038/s41590-023-01655-2. Online ahead of print. Regulatory T cell-derived IL-1Ra suppresses the innate response to respiratory viral infection
Jason W Griffith[SUP] 1 2 [/SUP], Lucas D Faustino[SUP] 1 3 [/SUP], Victoria I Cottrell[SUP] 1 3 [/SUP], Keshav Nepal[SUP] 1 3 [/SUP], Lida P Hariri[SUP] 2 4 [/SUP], Rebecca Suet-Yan Chiu[SUP] 1 3 [/SUP], Michael C Jones[SUP] 1 3 [/SUP], Amélie Julé[SUP] 5 [/SUP], Cem Gabay[SUP] 6 [/SUP], Andrew D Luster[SUP] 7 8 [/SUP]
Affiliations
Regulatory T (T[SUB]reg[/SUB]) cell modulation of adaptive immunity and tissue homeostasis is well described; however, less is known about T[SUB]reg[/SUB] cell-mediated regulation of the innate immune response. Here we show that deletion of ST2, the receptor for interleukin (IL)-33, on T[SUB]reg[/SUB] cells increased granulocyte influx into the lung and increased cytokine production by innate lymphoid and γδ T cells without alteration of adaptive immunity to influenza. IL-33 induced high levels of the interleukin-1 receptor antagonist (IL-1Ra) in ST2[SUP]+[/SUP] T[SUB]reg[/SUB] cells and deletion of IL-1Ra in T[SUB]reg[/SUB] cells increased granulocyte influx into the lung. T[SUB]reg[/SUB] cell-specific deletion of ST2 or IL-1Ra improved survival to influenza, which was dependent on IL-1. Adventitial fibroblasts in the lung expressed high levels of the IL-1 receptor and their chemokine production was suppressed by T[SUB]reg[/SUB] cell-produced IL-1Ra. Thus, we define a new pathway where IL-33-induced IL-1Ra production by tissue T[SUB]reg[/SUB] cells suppresses IL-1-mediated innate immune responses to respiratory viral infection.
. 2023 Nov 9.
doi: 10.1038/s41590-023-01655-2. Online ahead of print. Regulatory T cell-derived IL-1Ra suppresses the innate response to respiratory viral infection
Jason W Griffith[SUP] 1 2 [/SUP], Lucas D Faustino[SUP] 1 3 [/SUP], Victoria I Cottrell[SUP] 1 3 [/SUP], Keshav Nepal[SUP] 1 3 [/SUP], Lida P Hariri[SUP] 2 4 [/SUP], Rebecca Suet-Yan Chiu[SUP] 1 3 [/SUP], Michael C Jones[SUP] 1 3 [/SUP], Amélie Julé[SUP] 5 [/SUP], Cem Gabay[SUP] 6 [/SUP], Andrew D Luster[SUP] 7 8 [/SUP]
Affiliations
- PMID: 37945820
- DOI: 10.1038/s41590-023-01655-2
Regulatory T (T[SUB]reg[/SUB]) cell modulation of adaptive immunity and tissue homeostasis is well described; however, less is known about T[SUB]reg[/SUB] cell-mediated regulation of the innate immune response. Here we show that deletion of ST2, the receptor for interleukin (IL)-33, on T[SUB]reg[/SUB] cells increased granulocyte influx into the lung and increased cytokine production by innate lymphoid and γδ T cells without alteration of adaptive immunity to influenza. IL-33 induced high levels of the interleukin-1 receptor antagonist (IL-1Ra) in ST2[SUP]+[/SUP] T[SUB]reg[/SUB] cells and deletion of IL-1Ra in T[SUB]reg[/SUB] cells increased granulocyte influx into the lung. T[SUB]reg[/SUB] cell-specific deletion of ST2 or IL-1Ra improved survival to influenza, which was dependent on IL-1. Adventitial fibroblasts in the lung expressed high levels of the IL-1 receptor and their chemokine production was suppressed by T[SUB]reg[/SUB] cell-produced IL-1Ra. Thus, we define a new pathway where IL-33-induced IL-1Ra production by tissue T[SUB]reg[/SUB] cells suppresses IL-1-mediated innate immune responses to respiratory viral infection.