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Fish NF‐κB couples TCR and IL‐17 signals to regulate ancestral T‐cell immune response against bacterial infection
Author(s) -
Wei Xiumei,
Li Cheng,
Zhang Yu,
Li Kang,
Li Jiaqi,
Ai Kete,
Li Kunming,
Zhang Jiansong,
Yang Jialong
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202002393rr
Subject(s) - fish <actinopterygii> , t cell receptor , immune system , biology , nf κb , t cell , immunology , microbiology and biotechnology , signal transduction , fishery
As fish constitute the first evolutionary group with primordial T cells, they are of importance for understanding the origin and evolution of adaptive immunity. Yet, the knowledge about how ancestral T cells function remains limited. Therefore, the teleost model Nile tilapia ( Oreochromis niloticus ) was used in this study to investigate the regulatory mechanisms of T‐cell immunity in fish. We identified an evolutionarily conserved canonical NF‐κB signaling pathway in Nile tilapia, which participates in primary adaptive immune response during Streptococcus agalactiae infection. Blockade of NF‐κB activity severely impairs T‐cell activation and expansion, rendering the animals more vulnerable to pathogen attack. Meanwhile, NF‐κB signaling is indispensable for fish T cells to produce IL‐17A during the antibacterial immune response. Moreover, IL‐17A binds its receptor IL‐17RA, initiates the ACT1–TRAF6–TAK1 axis, and triggers NF‐κB‐dependent T‐cell activation, thus forming a positive feedback loop of T‐cell immunity in Nile tilapia. Furthermore, IL‐17A seems to promote innate immunity by regulating pro‐inflammatory cytokines via TRAF6–NF–κB axis, indicating the presence of an NF‐κB‐dependent IL‐17A signaling pathway for coordinating adaptive and innate immunity in fish. Our results suggest that fish NF‐κB couples TCR and IL‐17 signals to modulate ancestral T‐cell immunity against bacterial infection, and the regulation of T‐cell immunity by NF‐κB and IL‐17 is a strategy that existed prior to the divergence of the tetrapod lineage from teleost fish. This study, therefore, provides a new perspective on the evolution of adaptive immunity.