Type I interferon–mediated autoimmune diseases: pathogenesis, diagnosis and targeted therapy
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Abstract:
Type I interferons (IFN-Is) are a group of molecules with pleiotropic effects on the immune system forming a crucial link between innate and adaptive immune responses. Apart from their important role in antiviral immunity, IFN-Is are increasingly recognized as key players in autoimmune CTDs such as SLE. Novel therapies that target IFN-I appear effective in SLE in early trials, but effectiveness is related to the presence of IFN-I biomarkers. IFN-I biomarkers may also act as positive or negative predictors of response to other biologics. Despite the high failure rate of clinical trials in SLE, subgroups of patients often respond better. Fully optimizing the potential of these agents is therefore likely to require stratification of patients using IFN-I and other biomarkers. This suggests the unified concept of type I IFN–mediated autoimmune diseases as a grouping including patients with a variety of different traditional diagnoses.Keywords:
Pathogenesis
Innate lymphoid cell
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Intrinsic immunity
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Immunosuppression
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The immune system is divided into innate and adaptive immunity. Either immunity consists of humoral and cellular responses, and immunity is maximized when both responses coordinately function. Adaptive immunity has been intensively studied, while it was only recently that we gained some understanding of innate immunity. In particular, cellular responses in innate immunity have been poorly understood compared with humoral responses. In addition, the mechanisms and roles of innate immune responses could be distinct between the organisms that possess both innate and adaptive immunity and those possessing only innate immunity. On the other hand, invading pathogenic microbes employ various strategies to inhibit the host immune system for their survival. I here summarize what needs to be known to gain a deeper understanding of the innate immune response. The readers are suggested to refer to the accompanying articles for more detailed description.
Intrinsic immunity
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Zoie immune system including innate immunity and adaptive immunity.Innate immune system is a general defense mechanism which is built up in the process of development and evolution of biological spe-cies,including tissue barrier function,cell-mediated immunity,and humor immunity.Innate immunocytes ale activated by the recognition of mode elements on the pathogen.The immunological effect is producedthronsh special signal transduction pathway:Earthworm belongs to invertebrate whose immune system lacks immunoglobulin and has not developed adaptive immunity.So earthworm protects itself tllrough innate immu-nity.
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Earthworm; Innate immunity; Nuelease
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Current dogma holds that the innate immune system primes the adaptive immune system in response to infection, which in turn amplifies innate responses in a positive loop to effectively control pathogens. Therefore, it is accepted in most cases that T-cell deficient hosts die of acute infection because of the impaired ability of the innate immune system to control pathogens. Recent studies, however, reveal that adaptive immune cells actively dampen initial innate responses. In contrast to current understanding, there is now evidence that an insufficient number of T cells results in loss of control of innate immune responses. This raises new questions regarding the, as of yet underappreciated, role of the adaptive immune system in early infection and inflammation.
Innate lymphoid cell
CCL18
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Intrinsic immunity
Innate lymphoid cell
CCL18
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Innate immunity recognizes invading micro-organisms and triggers a host defence response.However,the molecular mechanism for innate immune recognition was unclear.Recently,a family of Toll-like receptors(TLRs) was identified,and crucial roles of these receptors in the recognition of microbial components have been elucidated.The TLR family consists of 11 members and will be expanding.Each TLR distinguishes between specific patterns of microbial components to provoke innate immune responses.The activation of innate immunity then leads to the development of antigen-specific adaptive immunity.Thus,TLRs control both innate and adaptive immune responses.
Intrinsic immunity
CCL18
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Innate immunity recognizes invading micro‐organisms and triggers a host defence response. However, the molecular mechanism for innate immune recognition was unclear. Recently, a family of Toll‐like receptors (TLRs) was identified, and crucial roles for these receptors in the recognition of microbial components have been elucidated. The TLR family consists of 10 members and will be expanding. Each TLR distinguishes between specific patterns of microbial components to provoke innate immune responses. The activation of innate immunity then leads to the development of antigen‐specific adaptive immunity. Thus, TLRs control both innate and adaptive immune responses.
Intrinsic immunity
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Innate lymphoid cell
Intrinsic immunity
Adaptive response
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The immune system of mammalians is organized around two components: the innate immunity and the adaptive immunity. Older in terms of evolution, the innate immune system constitutes the first line of defense against microorganisms. This system is supplemented by the adaptive immunity, which is more recent in terms of evolution and provides the basis of immunological memory. Both the adaptive and innate immune systems are composed of a cellular and a humoral arm acting in a complementary and coordinated manner to regulate the innate response.
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