Vasoactive intestinal peptide promotes host defense against enteric pathogens by modulating the recruitment of group 3 innate lymphoid cells

Yu, Hong; Yang, Hyungjun; Allaire, Joannie M.; Ma, Cun‐Gen; Graef, Franziska A.; Mortha, Arthur; Liang, Q; Bosman, Else S.; Reid, Gavin D.; Waschek, James A.; Osborne, Lisa C.; Sokol, Harry; Vallance, Bruce A.; Jacobson, Kevan

doi:10.1073/pnas.2106634118

Cited by 38 publications

(39 citation statements)

References 69 publications

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“…In vivo GPR183 deficiency results in disorganized distribution of ILC3 in mesenteric lymph nodes and reduces ILC3 accumulation in the intestine, and thus GPR183-deficient mice are more susceptible to infection by pathogenic intestinal bacteria [80]. In addition, ILC3 expresses vasoactive intestinal peptide (VIP) receptor 2 (VPAC2), and the VIP was identified to enhance resistance to murine Citrobacter infection by promoting CCR9 expression of ILC3 and intestinal recruitment [81].…”

Section: Intestinal Immune Cells and Their Secreted Substancesmentioning

confidence: 99%

Bacterial and Viral Co-Infection in the Intestine: Competition Scenario and Their Effect on Host Immunity

Lian

Liu

et al. 2022

IJMS

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Bacteria and viruses are both important pathogens causing intestinal infections, and studies on their pathogenic mechanisms tend to focus on one pathogen alone. However, bacterial and viral co-infections occur frequently in clinical settings, and infection by one pathogen can affect the severity of infection by another pathogen, either directly or indirectly. The presence of synergistic or antagonistic effects of two pathogens in co-infection can affect disease progression to varying degrees. The triad of bacterial–viral–gut interactions involves multiple aspects of inflammatory and immune signaling, neuroimmunity, nutritional immunity, and the gut microbiome. In this review, we discussed the different scenarios triggered by different orders of bacterial and viral infections in the gut and summarized the possible mechanisms of synergy or antagonism involved in their co-infection. We also explored the regulatory mechanisms of bacterial–viral co-infection at the host intestinal immune interface from multiple perspectives.

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Section: Intestinal Immune Cells and Their Secreted Substancesmentioning

confidence: 99%

Bacterial and Viral Co-Infection in the Intestine: Competition Scenario and Their Effect on Host Immunity

Lian

Liu

et al. 2022

IJMS

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“…ILC3 have been described to express the transcription factor (TF) RORgT and can be divided into two functional subsets: NKp44 -ILC3 secreting IL-17A and NKp44 + ILC3 secreting IL-22 (3,4). The latter have been recognized to be essential for promoting tissue integrity, maintaining barrier functions, and promoting homeostasis (3,5), especially within the gastrointestinal (GI) tract. Secretion of IL-22 seems to play a key role for these functional properties (3).…”

Section: Introductionmentioning

confidence: 99%

Efficient In Vitro Generation of IL-22-Secreting ILC3 From CD34+ Hematopoietic Progenitors in a Human Mesenchymal Stem Cell Niche

et al. 2021

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Innate lymphoid cells (ILCs) and in particular ILC3s have been described to be vital for mucosal barrier functions and homeostasis within the gastrointestinal (GI) tract. Importantly, IL-22-secreting ILC3 have been implicated in the control of inflammatory bowel disease (IBD) and were shown to reduce the incidence of graft-versus-host disease (GvHD) as well as the risk of transplant rejection. Unfortunately, IL-22-secreting ILC3 are primarily located in mucosal tissues and are not found within the circulation, making access to them in humans challenging. On this account, there is a growing desire for clinically applicable protocols for in vitro generation of effector ILC3. Here, we present an approach for faithful generation of functionally competent human ILC3s from cord blood-derived CD34+ hematopoietic progenitors on layers of human mesenchymal stem cells (MSCs) generated in good manufacturing practice (GMP) quality. The in vitro-generated ILC3s phenotypically, functionally, and transcriptionally resemble bona fide tissue ILC3 with high expression of the transcription factors (TF) RorγT, AHR, and ID2, as well as the surface receptors CD117, CD56, and NKp44. Importantly, the majority of ILC3 belonged to the desired effector subtype with high IL-22 and low IL-17 production. The protocol thus combines the advantages of avoiding xenogeneic components, which were necessary in previous protocols, with a high propensity for generation of IL-22-producing ILC3. The present approach is suitable for the generation of large amounts of ILC3 in an all-human system, which could facilitate development of clinical strategies for ILC3-based therapy in inflammatory diseases and cancer.

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“…Interestingly, the gut microbiota contributed to control of this circuit, as antibiotic treatment partially restored ILC3 abundance and constrained cytokine production in circadian-disrupted mice ( 195 ). In mice, VIP promotes ILC3 intestinal recruitment and maintains expression of gut-homing receptor CCR9 ( 196 ). Talbot et al reported a feeding-induced inhibition of ILC3s by VIPergic neurons, regulating mucosal immunity by dampening IL-22-induced antimicrobial peptide production in exchange for enhanced absorptive capacity of the intestinal epithelium marked by increased fatty acid transporter ( Fabp2 ) expression ( 197 ).…”

Section: Ilcs In the Intestinementioning

confidence: 99%

Tissue-Dependent Adaptations and Functions of Innate Lymphoid Cells

et al. 2022

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Tissue-resident immune cells reside in distinct niches across organs, where they contribute to tissue homeostasis and rapidly respond to perturbations in the local microenvironment. Innate lymphoid cells (ILCs) are a family of innate immune cells that regulate immune and tissue homeostasis. Across anatomical locations throughout the body, ILCs adopt tissue-specific fates, differing from circulating ILC populations. Adaptations of ILCs to microenvironmental changes have been documented in several inflammatory contexts, including obesity, asthma, and inflammatory bowel disease. While our understanding of ILC functions within tissues have predominantly been based on mouse studies, development of advanced single cell platforms to study tissue-resident ILCs in humans and emerging patient-based data is providing new insights into this lymphocyte family. Within this review, we discuss current concepts of ILC fate and function, exploring tissue-specific functions of ILCs and their contribution to health and disease across organ systems.

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Vasoactive intestinal peptide promotes host defense against enteric pathogens by modulating the recruitment of group 3 innate lymphoid cells

Cited by 38 publications

References 69 publications

Bacterial and Viral Co-Infection in the Intestine: Competition Scenario and Their Effect on Host Immunity

Bacterial and Viral Co-Infection in the Intestine: Competition Scenario and Their Effect on Host Immunity

Efficient In Vitro Generation of IL-22-Secreting ILC3 From CD34+ Hematopoietic Progenitors in a Human Mesenchymal Stem Cell Niche

Tissue-Dependent Adaptations and Functions of Innate Lymphoid Cells

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