New paradigm of B-cell biology regarding the elucidation of a new mechanism of tissue fibrosis in IgG4-related disease

Nakase, Hiroshi; Ishigami, Keiichi

doi:10.1016/j.jaci.2020.01.004

Cited by 2 publications

(2 citation statements)

References 11 publications

(12 reference statements)

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“…Both IgG4RD and CD have shared mechanisms that converge on the formation of plasmablast-rich germinal centers. This convergence may finally relate to fibrosis through the plasmablast-mediated release of PDGF as de-192 DOI: 10.1159/000521259 scribed above, with PDGF causing fibroblast activation and proliferation, leading to fibrosis [73,[79][80][81][82][83][84]. Fibrosis has been reported within and surrounding germinal centers containing IgG4 plasma cells in both IgG4RD and other inflammatory conditions, potentially providing evidence of plasma cell-induced fibroplasia [110][111][112][113][114].…”

Section: The Pathogenic Role Of Igg4 Plasmablasts In Fibroplasiamentioning

confidence: 99%

“…Further, these cells may directly contribute to the fibrosis seen in IgG4RD. Plasmablasts may secrete plateletderived growth factor (PDGF), which is known to activate fibroblasts and thus significantly contribute to fibrosis [73][74][75][76][77][78] The central role of these plasmablasts in IgG4RD is emphasized by the efficacy of rituxumab in disease treatment, and disease flares coinciding with an increase in IgG4 producing plasmablasts [72,73,[79][80][81][82][83][84].…”

Section: Igg4 Overviewmentioning

confidence: 99%

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The Possible Pathogenic Role of IgG4-Producing Plasmablasts in Stricturing Crohn’s Disease

Bushara¹,

Escobar²,

Weinberg³

et al. 2022

Pathobiology

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Background: Crohn’s disease (CD) is a condition on the spectrum of inflammatory bowel disease that affects up to 20 people per 100,000 in the US annually, and with incidence increasing. One of the most significant sources of morbidity in CD is the formation of strictures, with resultant intestinal blockage a common indication for hospitalization and surgical intervention in these patients. The pathophysiology of stricture formation is not fully understood. However, the fibroplasia that leads to fibrostenotic stricture formation may have shared pathophysiology with IgG4-related fibrosis. Summary: Initial intestinal inflammation recruits innate immune cells, such as neutrophils, that secrete IL-1β and IL-23, which induces a type 17 CD4+ T-helper T-cell (Th17)-mediated adaptive immune response. These CD4+ Th17 T cells also contribute to inflammation by secreting proinflammatory cytokines such as IL-17 and IL-21. IL-21 recruits and stimulates CD4+ T follicular helper (Tfh) cells, which secrete more IL-21. This causes ectopic germinal center formation, recruiting and stimulating naïve B cells. The IL-17 and IL-21 produced by Th17 cells and Tfh cells also induce IgG4 plasmablast differentiation. Finally, these IgG4-producing plasmablasts secrete platelet-derived growth factor (PDGF), which activates local PDGF-receptor expressing fibroblasts and myofibroblasts, resulting in uncontrolled fibroplasia.

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