scholarly journals Innate Immune Signaling Induces IL-7 Production, Early Inflammatory Responses, and Sjögren's-Like Dacryoadenitis in C57BL/6 Mice

2015 ◽  
Vol 56 (13) ◽  
pp. 7831 ◽  
Author(s):  
Jing Zhou ◽  
Jun-O, Jin ◽  
Juan Du ◽  
Qing Yu
Keyword(s):  
Inflammatory Responses ◽  
Innate Immune ◽  
Immune Signaling ◽  
Innate Immune Signaling

scholarly journals Interleukin-37 regulates innate immune signaling in human and mouse colonic organoids

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joannie M. Allaire ◽  
Anita Poon ◽  
Shauna M. Crowley ◽  
Xiao Han ◽  
Zohreh Sharafian ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Individual Variability ◽  
Innate Immune ◽  
Negative Regulator ◽  
Intestinal Epithelial ◽  
Immune Signaling ◽  
Strong Expression ◽  
Innate Immune Signaling ◽  
Close Proximity ◽  
Species Specific

AbstractIntestinal epithelial cells (IEC) reside in close proximity to the gut microbiota and are hypo-responsive to bacterial products, likely to prevent maladaptive inflammatory responses. This is in part due to their strong expression of Single Ig IL-1 related receptor (SIGIRR), a negative regulator of interleukin (IL)-1 and toll-like receptor signaling. IL-37 is an anti-inflammatory cytokine that inhibits innate signaling in diverse cells by signaling through SIGIRR. Despite the strong expression of SIGIRR by IEC, few studies have examined whether IL-37 can suppress their innate immune signaling. We characterized innate immune responses of human and murine colonoids to bacteria (FliC, LPS) and host (IL-1β) products and the role of IL-37/SIGIRR in regulating these responses. We demonstrated that human colonoids responded only to FliC, but not to LPS or IL-1β. While colonoids derived from different donors displayed significant inter-individual variability in the magnitude of their innate responses to FliC stimulation, all colonoids released a variety of chemokines. Interestingly, IL-37 attenuated these responses through inhibition of p38 and NFκB signaling pathways. We determined that this suppression by IL-37 was SIGIRR dependent, in murine organoids. Along with species-specific differences in IEC innate responses, we show that IL-37 can promote IEC hypo-responsiveness by suppressing inflammatory signaling.

scholarly journals Interleukin-37 Regulates Innate Immune Signaling in Human and Mouse Colonic Organoids

2020 ◽  
Author(s):  
Joannie Allaire ◽  
Anita Poon ◽  
Shauna Crowley ◽  
Xiao Han ◽  
Navjit Moore ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Individual Variability ◽  
Innate Immune ◽  
Negative Regulator ◽  
Intestinal Epithelial ◽  
Immune Signaling ◽  
Strong Expression ◽  
Innate Immune Signaling ◽  
Close Proximity ◽  
Species Specific

Abstract Intestinal epithelial cells (IEC) reside in close proximity to the gut microbiota and are hypo-responsive to bacterial products, likely to prevent maladaptive inflammatory responses. This is in part due to their strong expression of Single Ig IL-1 related receptor (SIGIRR), a negative regulator of interleukin (IL)-1 and toll-like receptor signaling. IL-37, an anti-inflammatory cytokine that inhibits innate signaling in diverse cells by signaling through SIGIRR. Despite the strong expression of SIGIRR by IEC, few studies have examined whether IL-37 can suppress their innate immune signaling. We characterized innate immune responses of human and murine colonoids to bacteria (FliC, LPS) and host (IL-1β) products and the role of IL-37/SIGIRR in regulating these responses. We demonstrated that human colonoids responded only to FliC, but not to LPS or IL-1β. While colonoids derived from different donors displayed significant inter-individual variability in the magnitude of their innate responses to FliC stimulation, all colonoids released a variety of chemokines. Interestingly, IL-37 attenuated these responses through inhibition of p38 and NFκB signaling pathways. We determined that this suppression by IL-37 was SIGIRR dependent, in murine organoids. Along with species-specific differences in IEC innate responses, we show that IL-37 can promote IEC hypo-responsiveness by supressing inflammatory signaling.

scholarly journals Critical Role for MyD88-Mediated Neutrophil Recruitment during Clostridium difficile Colitis

2012 ◽  
Vol 80 (9) ◽  
pp. 2989-2996 ◽  
Author(s):  
Irene Jarchum ◽  
Mingyu Liu ◽  
Chao Shi ◽  
Michele Equinda ◽  
Eric G. Pamer
Keyword(s):  
Clostridium Difficile ◽  
Inflammatory Responses ◽  
Adaptor Protein ◽  
Neutrophil Recruitment ◽  
Innate Immune ◽  
Antibiotic Administration ◽  
Immune Signaling ◽  
Content Type ◽  
Innate Immune Signaling ◽  
Deficient Mice

ABSTRACTClostridium difficilecan infect the large intestine and cause colitis when the normal intestinal microbiota is altered by antibiotic administration. Little is known about the innate immune signaling pathways that marshal inflammatory responses toC. difficileinfection and whether protective and pathogenic inflammatory responses can be dissociated. Toll-like receptors predominantly signal via the MyD88 adaptor protein and are important mediators of innate immune signaling in the intestinal mucosa. Here, we demonstrate that MyD88-mediated signals trigger neutrophil and CCR2-dependent Ly6Chimonocyte recruitment to the colonic lamina propria (cLP) during infection, which prevent dissemination of bystander bacteria to deeper tissues. Mortality is markedly increased in MyD88-deficient mice followingC. difficileinfection, as are parameters of mucosal tissue damage and inflammation. Antibody-mediated depletion of neutrophils markedly increases mortality, while attenuated recruitment of Ly6Chimonocytes in CCR2-deficient mice does not alter the course ofC. difficileinfection. Expression of CXCL1, a neutrophil-recruiting chemokine, is impaired in the cLP of MyD88−/−mice. Our studies suggest that MyD88-mediated signals promote neutrophil recruitment by inducing expression of CXCL1, thereby providing critical early defense againstC. difficile-mediated colitis.

scholarly journals Innate Immune Signaling and Its Role in Metabolic and Cardiovascular Diseases

2019 ◽  
Vol 99 (1) ◽  
pp. 893-948 ◽  
Author(s):  
Meng Xu ◽  
Peter P. Liu ◽  
Hongliang Li
Keyword(s):  
Transcription Factors ◽  
Immune System ◽  
Innate Immune System ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Immune Signaling ◽  
Cardiometabolic Diseases ◽  
Innate Immune Signaling ◽  
Cardiometabolic Disorders ◽  
Signaling Components

The innate immune system is an evolutionarily conserved system that senses and defends against infection and irritation. Innate immune signaling is a complex cascade that quickly recognizes infectious threats through multiple germline-encoded cell surface or cytoplasmic receptors and transmits signals for the deployment of proper countermeasures through adaptors, kinases, and transcription factors, resulting in the production of cytokines. As the first response of the innate immune system to pathogenic signals, inflammatory responses must be rapid and specific to establish a physical barrier against the spread of infection and must subsequently be terminated once the pathogens have been cleared. Long-lasting and low-grade chronic inflammation is a distinguishing feature of type 2 diabetes and cardiovascular diseases, which are currently major public health problems. Cardiometabolic stress-induced inflammatory responses activate innate immune signaling, which directly contributes to the development of cardiometabolic diseases. Additionally, although the innate immune elements are highly conserved in higher-order jawed vertebrates, lower-grade jawless vertebrates lack several transcription factors and inflammatory cytokine genes downstream of the Toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) pathways, suggesting that innate immune signaling components may additionally function in an immune-independent way. Notably, recent studies from our group and others have revealed that innate immune signaling can function as a vital regulator of cardiometabolic homeostasis independent of its immune function. Therefore, further investigation of innate immune signaling in cardiometabolic systems may facilitate the discovery of new strategies to manage the initiation and progression of cardiometabolic disorders, leading to better treatments for these diseases. In this review, we summarize the current progress in innate immune signaling studies and the regulatory function of innate immunity in cardiometabolic diseases. Notably, we highlight the immune-independent effects of innate immune signaling components on the development of cardiometabolic disorders.

scholarly journals Native and aspirin-triggered lipoxins control innate immunity by inducing proteasomal degradation of TRAF6

2008 ◽  
Vol 205 (5) ◽  
pp. 1077-1086 ◽  
Author(s):  
Fabiana S. Machado ◽  
Lísia Esper ◽  
Alexandra Dias ◽  
Rajat Madan ◽  
YuanYuan Gu ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Proteasomal Degradation ◽  
Innate Immune ◽  
Cytokine Signaling ◽  
Immune Signaling ◽  
Innate Immune Signaling

Innate immune signaling is critical for the development of protective immunity. Such signaling is, perforce, tightly controlled. Lipoxins (LXs) are eicosanoid mediators that play key counterregulatory roles during infection. The molecular mechanisms underlying LX-mediated control of innate immune signaling are of interest. In this study, we show that LX and aspirin (ASA)-triggered LX (ATL) inhibit innate immune signaling by inducing suppressor of cytokine signaling (SOCS) 2–dependent ubiquitinylation and proteasome-mediated degradation of TNF receptor–associated factor (TRAF) 2 and TRAF6, which are adaptor molecules that couple TNF and interleukin-1 receptor/Toll-like receptor family members to intracellular signaling events. LX-mediated degradation of TRAF6 inhibits proinflammatory cytokine production by dendritic cells. This restraint of innate immune signaling can be ablated by inhibition of proteasome function. In vivo, this leads to dysregulated immune responses, accompanied by increased mortality during infection. Proteasomal degradation of TRAF6 is a central mechanism underlying LX-driven immune counterregulation, and a hitherto unappreciated mechanism of action of ASA. These findings suggest a new molecular target for drug development for diseases marked by dysregulated inflammatory responses.

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