Allergic rhinitis and asthma are common chronic inflammatory diseases of the nasal mucus membranes and the upper airways with a high prevalence in Western countries. In addition to maladaptive T-helper type 2 (Th2) immunity, Th17 cells can drive the inflammatory responses in both diseases. Several reports have shown that the complement system is activated locally and systemically in allergic rhinitis and/or allergic asthma patients. Importantly, recent findings in experimental models of allergic rhinitis and allergic asthma suggest that the complement cleavage products complement 3a and complement 5a and the activation of their corresponding receptors in antigen-presenting cells regulate the development of maladaptive Th2 and Th17 immunity. These findings in experimental asthma are corroborated by genome-wide searches and candidate gene studies in humans. We discuss recent findings in experimental and human allergic airway diseases suggesting that complement may serve as a new diagnostic and therapeutic target for both disorders.
"The work on CD46-mediated signals on CD4 + T cells is beginning to give insight into the role of complement in human Th1 induction. A wealth of work establishes also a clear role for complement, and particularly for the anaphylatoxins, in the induction or regulation of Th17, natural regulatory T cell and Th2 responses – however, here, the majority of data in regards to the complement-mediated signalling pathways are currently derived from mouse models . Studies performed in pertinent animal models show that C5a affects the generation and modulation of proinflammatory T cell effector responses of the Th17 type by regulating IL-6 and IL- 1␤ produced by dendritic cells (DCs) and/or macrophages . "
[Show abstract][Hide abstract] ABSTRACT: The complement system is among the evolutionary oldest 'players' of the immune system. It was discovered in 1896 by Jules Bordet as a heat-labile fraction of the serum responsible for the opsonisation and subsequent killing of bacteria. The decades between the 1920s and 1990s then marked the discovery and biochemical characterization of the proteins comprising the complement system. Today, complement is defined as a complex system consisting of more than 30 membrane-bound and soluble plasma proteins, which are activated in a cascade-like manner, very similarly to the caspase proteases and blood coagulation systems. Complement is engrained in the immunologist's mind as a serum-effective, quintessential part of innate immunity, vitally required for the detection and removal of pathogens or other dangerous entities. Three decades ago, this rather confined definition was challenged and then refined when it was shown that complement participates vitally in the induction and regulation of B cell responses, thus adaptive immunity. Similarly, research work published in more recent years supports an equally important role for the complement system in shaping T cell responses. Today, we are again facing paradigm shifts in the field: complement is actively involved in the negative control of T cell effector immune responses, and thus, by definition in immune homeostasis. Further, while serum complement activity is without doubt fundamental in the defence against invading pathogens, local immune cell-derived production of complement emerges as key mediator of complement's impact on adaptive immune responses. And finally, the impact of complement on metabolic pathways and the crosstalk between complement and other immune effector systems is likely more extensive than previously anticipated and is fertile ground for future discoveries. In this review, we will discuss these emerging new roles of complement, with a focus on Th1 cell biology.
Seminars in Immunology 05/2013; 25(1). DOI:10.1016/j.smim.2013.04.012 · 5.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the complement system is thought to be mainly involved in innate immunity and in the humoral arm of adaptive responses, evidence implicating that complement impacts T cell responses are accumulating recently. The role of the various activation products of the major complement component C3 were mainly studied so far in animal systems, and investigations regarding the effect of different C3-fragments on human T cells are sparse. Here we show that anti-CD3 activated human T lymphocytes derived from the blood and tonsil of healthy individuals produce C3, and the major cleavage fragment that appears on the T cell surface is iC3b. Based on studies carried out in allogenic system we demonstrate that the T cell membrane bound iC3b binds to the CR3 and probably to CR4 receptors expressed on monocyte-derived dendritic cells, and this interaction leads to significantly enhanced T-cell proliferation. Since neither C3aR and nor C3a binding could be detected on the membrane of anti-CD3 activated T cells, our findings indicate that in humans – in contrast to mice – the C3a peptide is most probably not involved directly in the T cell activation process.
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