Front Pharmacol 2024 Aug 13:15:1450558. doi: 10.3389/fphar.2024.1450558.
AIG는 immunologic disorder로 다양한 pro & anti-inflammatory cytokines 이 존재하고, 이들을 조절함으로서 치료할 수 있지 않을까 생각됩니다. 최근까지 보고된 pathogenesis와 관련된 cytokines, 그리고 이에 대한 pathomechanism과 현재까지 나온 therapeutic options을 살펴 본 내용입니다.
Introduction
여기서 언급된 H. pylori (HP) 와의 연관성 인데요..
The relationship between HP infection and the pathogenesis of AIG remains unclear. HP infection may exacerbate AIG, as the destruction of parietal cells caused by HP related inflammation could expose molecular patterns of the H+/K+ ATPase pump. A case report demonstrated that HP-related gastritis ultimately transitioned into AIG and that the progression of AIG led to the spontaneous disappearance of the HP infection due to worsening gastric atrophy. Conversely, murine AIG was promoted by a CD4+ Th-1 response, which appears to be downregulated in mice infected with HP due to Th-2 immune responses and transforming growth factor β. This is consistent with a recent case report in a woman with HP-related gastritis who developed AIG after eradication therapy, with a rapid progression of the atrophic pattern in the corpus within 3 years. These data suggest that HP gastritis may have a suppressive effect on AIG pathogenesis. Supporting this hypothesis, the prevalence of AIG is very low in Asian countries, where the prevalence of HP infection is high.
작년 2023년 KDDW poster에서 Hp 감염된 AIG 환자에서의 내시경으로 관찰 된 위축의 진행 속도가 Hp 감염되지 않았던 환자에 비해 느리게 진행되었다는 연구 결과가 있는데, 이 내용과 유사한 것 같습니다. Hp는 아무래도 atrophy가 진행되면 본인들이 활동하거나 번식할 공간이 줄어들게 되기 때문에 host의 immune system에 관여하여 AIG에 의한 inflammatory process를 늦추는 것 같습니다.
현재까지 pathogenesis of AIG는 CD4+ Th-1 response와 autoreactivity of Th-1 cells이 관여하는 것으로 보입니다. 또한, Th1 dependent activation of human gastric cytotoxic mechanisms with IFN and TNFα production이 핵심적인 mechanisms of human autoimmune gastritis의 inflammatory damaging을 주는 것으로 보입니다.
This review aims to recapitulate the role of the major cytokines that are dysregulated in AIG, shedding the light on the contribution of each cytokine to the disease, with the aim to finally highlight potential novel therapeutics for AIG.
Figure 1. Cytokines involved in autoimmune gastritis. Several pro- and anti- inflammatory cytokines are produced by activated autoreactive T cells, macrophages and B cells, amplifying the immune response and favoring parietal cell apoptosis, the disruption of epithelial barrier and fibrosis. In red (pejorative cytokines), in green (protective cytokines) and in yellow (real contribution to be define) (IFNγ, interferon-gamma; TNF-α, TumorNecrosis Factor-α; IL-21, Interleukin-21; IL-15, Interleukin-15; TGFβ, Transforming Growth Factor-β; IL-27, Interleukin-27; IL-10, Interleukin-10; IL-13, Interleukin-13; IL-33, Interleukin-33; TSLP, Thymic Stromal Lymphopoietin; IL-17, Interleukin-17; IL-8, Interleukin-8; eNAMPT, extracellular nicotinamide phosphoribosyl transferase; IL-6, Interleukin-6; PMN, polymorphonuclear neutrophils).
Table 1. Summary of the current knowledge on cytokine roles, levels and possible future medications in AIG.
In summary, although there are no approved biological therapies for AIG yet, exploring these cytokine targets could lead to new treatment options. Further research is crucial to validate the contribution of these cytokines in AIG and to develop effective therapeutics trategies.
Figure 2. Molecular mechanisms elicit by the main pejorative cytokines involved in autoimmune gastritis.
(IFNγ, interferon-gamma; TNF-α, Tumor Necrosis Factor-α; IL-21, Interleukin-21; IL-13, Interleukin-13; IL-17A, Interleukin-17A; eNAMPT, extracellular nicotinamide phosphoribosyl transferase; JAK, Janus kinase; JNK, c-JunN-terminal kinases; ERK, Extracellular signal-regulated kinases; P38, mitogen-activated protein kinases; NF-κB, nuclear factor kappa light-chain-enhancer of activated B cells; STAT, Signal transducer and activator of transcription.)
Abstract
Autoimmune gastritis (AIG) is an autoimmune disorder characterized by the destruction of gastric parietal cells and atrophy of the oxyntic mucosa which induces intrinsic factor deficiency and hypo-achlorhydria. AIG predominantly affects the antral mucosa with AIG patients experiencing increased inflammation and a predisposition toward the development of gastric adenocarcinoma and type I neuroendocrine tumors. The exact pathogenesis of this autoimmune disorder is incompletely understood although dysregulated immunological mechanisms appear to major contributors. This review of autoimmune gastritis, an unmet medical need, summarizes current knowledge on pro- and anti-inflammatory cytokines and strategies for the discovery of novel biomarkers and potential pharmacological targets.
Keywords: autoimmune atrophic gastritis; cytokine; immune system; inflammation; therapy.
Front Pharmacol 2024 Aug 13:15:1450558. doi: 10.3389/fphar.2024.1450558.
AIG는 immunologic disorder로 다양한 pro & anti-inflammatory cytokines 이 존재하고, 이들을 조절함으로서 치료할 수 있지 않을까 생각됩니다. 최근까지 보고된 pathogenesis와 관련된 cytokines, 그리고 이에 대한 pathomechanism과 현재까지 나온 therapeutic options을 살펴 본 내용입니다.
Introduction
여기서 언급된 H. pylori (HP) 와의 연관성 인데요..
The relationship between HP infection and the pathogenesis of AIG remains unclear. HP infection may exacerbate AIG, as the destruction of parietal cells caused by HP related inflammation could expose molecular patterns of the H+/K+ ATPase pump. A case report demonstrated that HP-related gastritis ultimately transitioned into AIG and that the progression of AIG led to the spontaneous disappearance of the HP infection due to worsening gastric atrophy. Conversely, murine AIG was promoted by a CD4+ Th-1 response, which appears to be downregulated in mice infected with HP due to Th-2 immune responses and transforming growth factor β. This is consistent with a recent case report in a woman with HP-related gastritis who developed AIG after eradication therapy, with a rapid progression of the atrophic pattern in the corpus within 3 years. These data suggest that HP gastritis may have a suppressive effect on AIG pathogenesis. Supporting this hypothesis, the prevalence of AIG is very low in Asian countries, where the prevalence of HP infection is high.
작년 2023년 KDDW poster에서 Hp 감염된 AIG 환자에서의 내시경으로 관찰 된 위축의 진행 속도가 Hp 감염되지 않았던 환자에 비해 느리게 진행되었다는 연구 결과가 있는데, 이 내용과 유사한 것 같습니다. Hp는 아무래도 atrophy가 진행되면 본인들이 활동하거나 번식할 공간이 줄어들게 되기 때문에 host의 immune system에 관여하여 AIG에 의한 inflammatory process를 늦추는 것 같습니다.
현재까지 pathogenesis of AIG는 CD4+ Th-1 response와 autoreactivity of Th-1 cells이 관여하는 것으로 보입니다. 또한, Th1 dependent activation of human gastric cytotoxic mechanisms with IFN and TNFα production이 핵심적인 mechanisms of human autoimmune gastritis의 inflammatory damaging을 주는 것으로 보입니다.
This review aims to recapitulate the role of the major cytokines that are dysregulated in AIG, shedding the light on the contribution of each cytokine to the disease, with the aim to finally highlight potential novel therapeutics for AIG.
Figure 1. Cytokines involved in autoimmune gastritis. Several pro- and anti- inflammatory cytokines are produced by activated autoreactive T cells, macrophages and B cells, amplifying the immune response and favoring parietal cell apoptosis, the disruption of epithelial barrier and fibrosis. In red (pejorative cytokines), in green (protective cytokines) and in yellow (real contribution to be define) (IFNγ, interferon-gamma; TNF-α, TumorNecrosis Factor-α; IL-21, Interleukin-21; IL-15, Interleukin-15; TGFβ, Transforming Growth Factor-β; IL-27, Interleukin-27; IL-10, Interleukin-10; IL-13, Interleukin-13; IL-33, Interleukin-33; TSLP, Thymic Stromal Lymphopoietin; IL-17, Interleukin-17; IL-8, Interleukin-8; eNAMPT, extracellular nicotinamide phosphoribosyl transferase; IL-6, Interleukin-6; PMN, polymorphonuclear neutrophils).
Table 1. Summary of the current knowledge on cytokine roles, levels and possible future medications in AIG.
In summary, although there are no approved biological therapies for AIG yet, exploring these cytokine targets could lead to new treatment options. Further research is crucial to validate the contribution of these cytokines in AIG and to develop effective therapeutics trategies.
Figure 2. Molecular mechanisms elicit by the main pejorative cytokines involved in autoimmune gastritis.
(IFNγ, interferon-gamma; TNF-α, Tumor Necrosis Factor-α; IL-21, Interleukin-21; IL-13, Interleukin-13; IL-17A, Interleukin-17A; eNAMPT, extracellular nicotinamide phosphoribosyl transferase; JAK, Janus kinase; JNK, c-JunN-terminal kinases; ERK, Extracellular signal-regulated kinases; P38, mitogen-activated protein kinases; NF-κB, nuclear factor kappa light-chain-enhancer of activated B cells; STAT, Signal transducer and activator of transcription.)
Abstract
Autoimmune gastritis (AIG) is an autoimmune disorder characterized by the destruction of gastric parietal cells and atrophy of the oxyntic mucosa which induces intrinsic factor deficiency and hypo-achlorhydria. AIG predominantly affects the antral mucosa with AIG patients experiencing increased inflammation and a predisposition toward the development of gastric adenocarcinoma and type I neuroendocrine tumors. The exact pathogenesis of this autoimmune disorder is incompletely understood although dysregulated immunological mechanisms appear to major contributors. This review of autoimmune gastritis, an unmet medical need, summarizes current knowledge on pro- and anti-inflammatory cytokines and strategies for the discovery of novel biomarkers and potential pharmacological targets.
Keywords: autoimmune atrophic gastritis; cytokine; immune system; inflammation; therapy.