TY - JOUR
T1 - A hierarchical role of IL-25 in ILC development and function at the lung mucosae following viral-vector vaccination
AU - Li, Z.
AU - Jackson, R. J.
AU - Ranasinghe, C.
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/8/9
Y1 - 2019/8/9
N2 - This study demonstrates that modulation of IL-25 and IL-33 cytokines responsible for innate lymphoid cell 2 (ILC2) activation/function can differentially regulate ILC profiles at the vaccination site, in a vaccine route-dependent manner. Specifically, recombinant fowlpox (rFPV) vector-based vaccine co-expressing an adjuvant that transiently sequestered IL-25 (FPV-HIV-IL-25 binding protein), delivered intramuscularly (i.m.) was able to induce significantly lower IL-25R+ ILC2-deived IL-13 and ILC1/ILC3-derived IFN-γ expression with significantly elevated IL-17A in muscle. In contrast, intranasal (i.n.) delivery was able to induce all three known ILC2 subsets (ST2/IL-33R+, IL-25R+, and TSLPR+ ILC2) to express varying amounts of IL-13 in lung, and also the TSLPR+ ILC2 to express IL-4, unlike the unadjuvanted control, which only showed ST2/IL-33R+ ILC2 to express IL-13. Interestingly, the sequestration of IL-25 in lung also induced a unique lineage− ST2/IL-33R− IL-25R− TSLPR− ILC2 population to express elevated IL-13 and IL-4. Moreover, both i.m. and, i.n. FPV-HIV-IL-25BP vaccination induced significantly elevated ILC1/ILC3-derived IL-17A in lung, indicating that ILC2 could directly impact ILC1/ILC3 activity. To our surprise, transient sequestration of IL-33 at the lung mucosae did not alter the lung ILC2 profiles or activity. These inhibitor studies showed that in the context of i.n. viral vector vaccination, IL-25 plays a predominant role in early ILC development/regulation than IL-33, and likely acts as a master regulator of ILC. Our previous findings have indicated that level of IL-4/IL-13 at the vaccination site impacts the quality/avidity of T cell immunity. Taken together data suggest that IL-25 binding protein could be used as an effective i.m. not an i.n. adjuvant to enhance quality of vaccine-specific T cell immunity. These findings evoke the notion that route-dependent manipulation of ILCs according to the target pathogen could be exploited to design more effective vaccines against chronic pathogens in the future.
AB - This study demonstrates that modulation of IL-25 and IL-33 cytokines responsible for innate lymphoid cell 2 (ILC2) activation/function can differentially regulate ILC profiles at the vaccination site, in a vaccine route-dependent manner. Specifically, recombinant fowlpox (rFPV) vector-based vaccine co-expressing an adjuvant that transiently sequestered IL-25 (FPV-HIV-IL-25 binding protein), delivered intramuscularly (i.m.) was able to induce significantly lower IL-25R+ ILC2-deived IL-13 and ILC1/ILC3-derived IFN-γ expression with significantly elevated IL-17A in muscle. In contrast, intranasal (i.n.) delivery was able to induce all three known ILC2 subsets (ST2/IL-33R+, IL-25R+, and TSLPR+ ILC2) to express varying amounts of IL-13 in lung, and also the TSLPR+ ILC2 to express IL-4, unlike the unadjuvanted control, which only showed ST2/IL-33R+ ILC2 to express IL-13. Interestingly, the sequestration of IL-25 in lung also induced a unique lineage− ST2/IL-33R− IL-25R− TSLPR− ILC2 population to express elevated IL-13 and IL-4. Moreover, both i.m. and, i.n. FPV-HIV-IL-25BP vaccination induced significantly elevated ILC1/ILC3-derived IL-17A in lung, indicating that ILC2 could directly impact ILC1/ILC3 activity. To our surprise, transient sequestration of IL-33 at the lung mucosae did not alter the lung ILC2 profiles or activity. These inhibitor studies showed that in the context of i.n. viral vector vaccination, IL-25 plays a predominant role in early ILC development/regulation than IL-33, and likely acts as a master regulator of ILC. Our previous findings have indicated that level of IL-4/IL-13 at the vaccination site impacts the quality/avidity of T cell immunity. Taken together data suggest that IL-25 binding protein could be used as an effective i.m. not an i.n. adjuvant to enhance quality of vaccine-specific T cell immunity. These findings evoke the notion that route-dependent manipulation of ILCs according to the target pathogen could be exploited to design more effective vaccines against chronic pathogens in the future.
KW - Adjuvants
KW - IL-13
KW - IL-17
KW - IL-25R
KW - IL-33R
KW - ILC
KW - Mucosal/systemic vaccination
KW - TSLPR
UR - http://www.scopus.com/inward/record.url?scp=85069731913&partnerID=8YFLogxK
U2 - 10.1016/j.jvacx.2019.100035
DO - 10.1016/j.jvacx.2019.100035
M3 - Article
SN - 2590-1362
VL - 2
JO - Vaccine: X
JF - Vaccine: X
M1 - 100035
ER -