Trained ILC3 responses promote intestinal defense

Abstract

Group 3 innate lymphoid cells (ILC3s) are innate immune effectors that contribute to host defense. Whether ILC3 functions are stably modified after pathogen encounter is unknown. Here, we assess the impact of a time-restricted enterobacterial challenge to long-term ILC3 activation in mice. We found that intestinal ILC3s persist for months in an activated state after exposure to Citrobacter rodentium . Upon rechallenge, these “trained” ILC3s proliferate, display enhanced interleukin-22 (IL-22) responses, and have a superior capacity to control infection compared with naïve ILC3s. Metabolic changes occur in C. rodentium –exposed ILC3s, but only trained ILC3s have an enhanced proliferative capacity that contributes to increased IL-22 production. Accordingly, a limited encounter with a pathogen can promote durable phenotypic and functional changes in intestinal ILC3s that contribute to long-term mucosal defense.

Impaired IL-23–dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency

“…S5 C ). We also showed that PBMCs from controls secreted IFN-γ in response to IL-12, IL-23, and a combination of IL-23 and IL-1β (known to potentiate IL-23; Serafini et al, 2022 ) as determined by multiplex ELISA ( Fig. 7 F ).…”

Intestinal Epithelial Heat Shock Protein 25/27 integrates host and microbial drivers of mucosal restitution following inflammatory injury

“…Using both in vitro and in vivo approaches, the latter involving cell specific Hsp25 gene-targeted deletion and overexpression murine models, we report that Hsp25/27 is an essential facilitator of the transcription factor STAT3 (Signal transducer and activator of transcription 3) which functions to converge many cooperative gut microbial and host signals that promote intestinal mucosal restitution following immune and inflammatory stress and injury. STAT3 has been shown to control cell growth, division, migration, and apoptosis to proinflammatory actions and its phosphorylation and activation by IL-22 promotes mucosal healing [35][36][37][38][39][40][41] . Conversely, STAT3 is involved in pro-inflammatory cytokine signaling through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway that is associated with autoimmune disorders and various cancers 42 .…”

A protocol to isolate bone marrow innate lymphoid cells for alymphoid mouse reconstitution

“…In contrast to T cells, ILC activity is not restricted to a specific antigen but does rely on the integration of environmental signals driving their effector functions ( Klose and Artis, 2020 ). Despite apparent redundancy, ILC and T cells play complementary roles with distinct temporal activity that enables them to eliminate pathogens and preserve tissue homeostasis ( Rankin et al., 2016 ; Serafini et al., 2022 ). Due to a significant overlap between T cell and ILC transcriptomic profiles ( Ercolano et al., 2020 ) and effector functions, it remains challenging to unravel the actions of individual genes regulators in ILC homeostasis through gene deletional targeting ( Cording et al., 2018 ).…”