The role of inflammation in autoimmune disease: a therapeutic target

Abstract

Autoimmune diseases (AIDs) are immune disorders whose incidence and prevalence are increasing year by year. AIDs are produced by the immune system's misidentification of self-antigens, seemingly caused by excessive immune function, but in fact they are the result of reduced accuracy due to the decline in immune system function, which cannot clearly identify foreign invaders and self-antigens, thus issuing false attacks, and eventually leading to disease. The occurrence of AIDs is often accompanied by the emergence of inflammation, and inflammatory mediators (inflammatory factors, inflammasomes) play an important role in the pathogenesis of AIDs, which mediate the immune process by affecting innate cells (such as macrophages) and adaptive cells (such as T and B cells), and ultimately promote the occurrence of autoimmune responses, so targeting inflammatory mediators/pathways is one of emerging the treatment strategies of AIDs. This review will briefly describe the role of inflammation in the pathogenesis of different AIDs, and give a rough introduction to inhibitors targeting inflammatory factors, hoping to have reference significance for subsequent treatment options for AIDs.

Keywords: B cells; T cells; autoimmunity; inflammation; pro-inflammatory factors.

Figure 1

The pathogenesis of RA. Antigen-presenting cells activate T cells and B cells to trigger adaptive immunity. B cells produce autoantibodies that stimulate macrophages to secrete pro-inflammatory factors and promote transcription of inflammatory genes. T cell differentiation into TH17 cells plays a pro-inflammatory role, and IL-4/IL-13 produced by TH2 cells triggers the activation of anti-inflammatory signaling pathways, and the production of anti-inflammatory factors and anti-inflammatory lipids is conducive to disease reversal. PD1 PD15, anti-inflammatory lipids. APCs, antigen-presenting cells. TCR, T cell receptor. TLR, Toll-like receptor.

Figure 2

The pathogenesis of SLE. The appearance of NETosis in neutrophils promotes the secretion of IFN-α/β by pDC cells to stimulate the body’s innate immunity and adaptive immunity, while the frontal interaction between inflammatory cells and lymphoid T and B cells results in the production of a large number of inflammatory factors. APCs, antigen-presenting cells. TCR, T cell receptor. BCR, B cell receptor. BAFFR, B-cell activating factor receptor. CRP, C-reactive protein; ESR, erythrocyte sedimentation rate.

Figure 3

The pathogenesis of SSc. Upregulation of vasoactive factors affects apoptosis of epithelial cells, followed by cytokines that stimulate the immune response in the body, and the inflammatory response that occurs eventually triggers the transformation of fibroblasts, leading to the formation of skin fibrosis. ECM, extracellular matrix. CXC, chemotaxis.

Figure 4

The pathogenesis of SS (take the lacrimal glands as an example). The cytokines produced by epithelial cells stimulate the secretion of inflammatory factors by monocytes and macrophages and the joint response of inflammasomes, which combine with the interaction between bound immune cells, ultimately leading to inflammation. NLRP3, inflammasomes. CXC, chemotaxis.

Figure 5

The pathogenesis of AS. ER stress triggered by the HLA-B27 gene may be the trigger for AS, and the T cell cross-reactivity triggered by the formed complex may also be one of the triggers. The IL-23/IL-17 pathway in the body plays an important role in the overall pathogenesis and is an important player in leading to inflammation and cartilage damage. MIF, macrophage migration inhibitor. TCR, T cell receptor.

Figure 6

The pathogenesis of AIH. The activation of T cells by antigen-presenting cells prompts them to differentiate into multiple cells, which act in tandem with B cells and innate immune cells by secreting different inflammatory factors to promote apoptosis and damage of liver cells, which eventually leads to the appearance of chronic hepatitis. Treg cells, regulatory T cells; DAMP, damage-related molecular patterns. APCs, antigen-presenting cells. CLT, Cytotoxic lymphoid T cells.

Figure 7

The pathogenesis of IBDs. The occurrence of IBD is often accompanied by immune disorders, intestinal flora disorders, and metabolic disorders, which are related to the imbalance regulation between inflammatory cells, immune cells, and intestinal groups. The damage of this intestinal epithelial cell triggers a cascading response by the immune system, and the various cytokines produced can trigger the destruction of the intestinal mucosal barrier, leading to the appearance of intestinal inflammation.CLT, Cytotoxic lymphoid T cells. CXC, chemotaxis.

Figure 8

The structure of small molecule inhibitors.