Immune dysregulation in immunoglobulin G4–related disease

Mitsui, Takashi; Koga, Risako; Nakamura, Seiji

doi:10.1016/j.jdsr.2022.12.002

Cited by 4 publications

(2 citation statements)

References 71 publications

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“…10 B ). Moreover, when considering causative cellular disease drivers, both the Lat Y136F DLSP and IgG4-RD are characterized by the accumulation in the SLO and lung of both Tfh cells capable of inducing IgG1/IgG4, and IgE autoantibodies causing systemic autoimmunity and of CD4 + CTL that by triggering apoptosis contributes to promote fibrosis and organ dysfunction ( Chen et al, 2019 ; Katz and Stone, 2022 ; Maehara et al, 2023 ; Munemura et al, 2022 ; Perugino and Stone, 2020 ). Akin to the results reported here for the Lat Y136F DLSP, treatment of IgG4-RD with CTLA-4-Ig (Abatacept) also reduced IgG4 and IgE levels ( Matza et al, 2022 ), emphasizing the contribution of CD28 co-stimulation to both Lat Y136F DLSP and IgG4-RD.…”

Section: Discussionmentioning

confidence: 99%

“…In view of this spectrum of histopathological manifestations and considering that mouse IgG1 constitutes the homologue of human IgG4, it has been suggested that the Lat Y136F DLSP constitutes a mouse model of human IgG4-related disease (IgG4-RD; Yamada et al, 2018 ), a fibro-inflammatory condition originally characterized by high levels of IgG4. The multiorgan tumor-like masses characteristic of IgG4-RD involve T follicular helper T cells (Tfh), CD4 + cytotoxic T lymphocytes (CTL), and IgG4 + PC, and lead to irreversible tissue damage ( Chen et al, 2019 ; Katz and Stone, 2022 ; Maehara et al, 2023 ; Perugino and Stone, 2020 ). Moreover, IgE is often increased in the serum of IgG4-RD patients ( Della Torre et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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Defective LAT signalosome pathology in mice mimics human IgG4-related disease at single-cell level

Joachim,

Aussel,

Gélard

et al. 2023

Journal of Experimental Medicine

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Mice with a loss-of-function mutation in the LAT adaptor (LatY136F) develop an autoimmune and type 2 inflammatory disorder called defective LAT signalosome pathology (DLSP). We analyzed via single-cell omics the trajectory leading to LatY136F DLSP and the underlying CD4+ T cell diversification. T follicular helper cells, CD4+ cytotoxic T cells, activated B cells, and plasma cells were found in LatY136F spleen and lung. Such cell constellation entailed all the cell types causative of human IgG4-related disease (IgG4-RD), an autoimmune and inflammatory condition with LatY136F DLSP-like histopathological manifestations. Most previously described T cell–mediated autoimmune manifestations require persistent TCR input. In contrast, following their first engagement by self-antigens, the autoreactive TCR expressed by LatY136F CD4+ T cells hand over their central role in T cell activation to CD28 costimulatory molecules. As a result, all subsequent LatY136F DLSP manifestations, including the production of autoantibodies, solely rely on CD28 engagement. Our findings elucidate the etiology of the LatY136F DLSP and qualify it as a model of IgG4-RD.

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