C5a receptor‐deficient dendritic cells promote induction of Treg and Th17 cells

Weaver, Donald J.; Reis, Edimara S.; Pandey, Manoj Kumar; Köhl, Gabriele; Harris, Nathaniel; Gérard, Craig; Köhl, Jörg

doi:10.1002/eji.200939333

Cited by 112 publications

(131 citation statements)

References 39 publications

(44 reference statements)

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“…Our results indicate that fusing trout C5a to G protein in the recombinant protein vaccine increased both the kinetics and longevity of the antibody response. In mammals, antigen presentation is augmented by C5aR signaling, resulting in a vigorous response of T cells, including Th1, Th2, Treg and Th17 [39,40]. Complement components have also been shown to enhance DC mediated CD8 þ T cell responses especially in antiviral immunity [21].…”

Section: Discussionmentioning

confidence: 99%

Complement C5a acts as molecular adjuvant in fish by enhancing antibody response to soluble antigen

LaPatra

et al. 2014

Fish & Shellfish Immunology

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Section: Discussionmentioning

confidence: 99%

Complement C5a acts as molecular adjuvant in fish by enhancing antibody response to soluble antigen

LaPatra

et al. 2014

Fish & Shellfish Immunology

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“…Being at the point of contact between APC and T cells, bidirectional signalling mediated by anaphylatoxins could thus ramp up the immune response. In this issue of European Journal of Immunology, Köhl and colleagues [13] give careful consideration to the possibility of interaction between C5aR signalling and other danger sensing pathways. This is a sound notion, given that infection initiates multiple danger signals, which are recognised by innate immune receptors on DC [14].…”

mentioning

confidence: 99%

“…This is a sound notion, given that infection initiates multiple danger signals, which are recognised by innate immune receptors on DC [14]. The authors [13] arrange for experiments to allow or deny C5aR signalling on mouse spleen DC, in the presence of TL2R stimulation (with PAM), and determine how well these manipulated DC loaded with OVA stimulate OVA-specific CD4 1 T cells. In full flight, antigen presentation is augmented by TLR2 and C5aR signalling, resulting in a vigorous Th1 response (Fig.…”

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confidence: 99%

Complement fragments C3a and C5a: The salt and pepper of the immune response

Sacks

2010

Eur J Immunol

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The influence of complement on B‐cell responses has been known for many years, but the notion that T‐cell recognition, expansion and differentiation are complement dependent has only recently gained impetus. DC, and to a lesser extent T cells, produce a range of complement components necessary for complement activation, and these cells also express receptors that detect complement‐activation products such as C3a and C5a (anaphylatoxins). In the absence of C3a‐receptor (C3aR) signalling, DC lose their capacity to induce potent Th1 responses against alloantigen and also favour the emergence of Treg. A study in this issue of the European Journal of Immunology not only spotlights the importance of C5aR signalling in DC interaction with T cells, but also shows how cooperation with other signalling pathways determines the outcome of T‐cell activation. Remove C5aR from the equation, TLR2‐stimulated DC induce naive CD4+ Th cells to undergo differentiation not only mainly to Th17 cells but also to Treg, via a TGF‐β‐dependent pathway. Thus, anaphylatoxins in conjunction with other danger signalling pathways modify the function of DC in antigen presentation and help to shape the primary immune response. Future work will need to address the impact of anaphylatoxins on protective immunity in vivo and determine the wider implications of anaphylatoxins for allo‐ and autoimmunity.

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“…In addition to their pro-inflammatory properties, these molecules regulate antigen-presenting cell functions and adaptive immune responses (Klos et al, 2009). Indeed, C3a and C5a have been shown to modulate the expression levels of MHC class II and costimulatory molecules on dendritic cells (Strainic et al, 2008;Weaver et al, 2010). C5b initiates the terminal phase of complement activation, i.e., the formation of the membrane-attack complex (MAC) in association with the C6, C7, C8 and 1-18 molecules of C9, which leads to the formation of pores in pathogen membranes (Bhakdi and Tranum-Jensen, 1991;Esser, 1991).…”

Section: Introductionmentioning

confidence: 99%

Molecular cloning and expression analysis of Pleurodeles waltl complement component C3 under normal physiological conditions and environmental stresses

Guéguinou

Huin-Schohn

Ouzren-Zarhloul

et al. 2014

Developmental & Comparative Immunology

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a b s t r a c tC3 is a component of the complement system that plays a central role in immunity, development and tissue regeneration. In this study, we isolated the C3 cDNA of the Iberian ribbed newt Pleurodeles waltl. This cDNA encodes a 1637 amino acid protein with an estimated molecular mass of 212.5 kDa. The deduced amino acid sequence showed that P. waltl C3 contains all the conserved domains known to be critical for C3 function. Quantitative real-time PCR (qRT-PCR) demonstrated that under normal physiological conditions, P. waltl C3 mRNA is expressed early during development because it is likely required for neurulation. Then, its expression increased as the immune system developed. In adults, the liver is the richest source of C3, though other tissues can also contribute. Further analysis of C3 expression demonstrated that C3 transcription increased when P. waltl larvae were exposed to pH or temperature stress, suggesting that environmental modifications might affect this animal's defenses against pathogens.

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C5a receptor‐deficient dendritic cells promote induction of Treg and Th17 cells

Abstract: C5a is a proinflammatory mediator that has recently been shown to regulate adaptive immune responses. Here we demonstrate that C5a receptor (C5aR) signaling in DC affects the development of Treg and Th17 cells.

Cited by 112 publications

References 39 publications

Complement C5a acts as molecular adjuvant in fish by enhancing antibody response to soluble antigen

Complement C5a acts as molecular adjuvant in fish by enhancing antibody response to soluble antigen

Complement fragments C3a and C5a: The salt and pepper of the immune response

Molecular cloning and expression analysis of Pleurodeles waltl complement component C3 under normal physiological conditions and environmental stresses

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