Shiv Pillai1, Cory Perugino1,2, Naoki Kaneko1,3. 1. Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge. 2. Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Massachusetts, Boston, Massachusetts, USA. 3. Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Abstract
PURPOSE OF REVIEW: To summarize recent advances in the understanding of the pathogenesis of IgG4-related disease. RECENT FINDINGS: Limited data exist to explain genetic susceptibility to IgG4-related disease and the underlying triggers for this disease have not yet been identified. Cytotoxic CD4 T cells and activated B cells infiltrate affected organs and express proinflammatory and profibrotic molecules. Antigen presented by activated B cells likely reactivates cytotoxic CD4 T cells in disease tissues and these T cells in turn induce the targeted apoptotic death of host cells in certain organs - which presumably present the same antigenic peptide on human leukocyte antigen class II molecules of relevance that was also presented on B cells during reactivation. A subsequent exaggerated tissue remodeling process is orchestrated by cytokines, chemokines, and enzymes secreted by both activated B cells and CD4CTLs. These molecules induce an overexuberant repair process resulting in fibrosis and loss of target organ function. SUMMARY: In IgG4-related disease, presumably self-reactive cytotoxic CD4 T cells infiltrate tissues, are reactivated by T cells and induce apoptotic death. Molecules secreted by activated B cells and by CD4CTLs drive an exaggerated wound healing response resulting in fibrosis and compromised tissue function.
PURPOSE OF REVIEW: To summarize recent advances in the understanding of the pathogenesis of IgG4-related disease. RECENT FINDINGS: Limited data exist to explain genetic susceptibility to IgG4-related disease and the underlying triggers for this disease have not yet been identified. Cytotoxic CD4 T cells and activated B cells infiltrate affected organs and express proinflammatory and profibrotic molecules. Antigen presented by activated B cells likely reactivates cytotoxic CD4 T cells in disease tissues and these T cells in turn induce the targeted apoptotic death of host cells in certain organs - which presumably present the same antigenic peptide on human leukocyte antigen class II molecules of relevance that was also presented on B cells during reactivation. A subsequent exaggerated tissue remodeling process is orchestrated by cytokines, chemokines, and enzymes secreted by both activated B cells and CD4CTLs. These molecules induce an overexuberant repair process resulting in fibrosis and loss of target organ function. SUMMARY: In IgG4-related disease, presumably self-reactive cytotoxic CD4 T cells infiltrate tissues, are reactivated by T cells and induce apoptotic death. Molecules secreted by activated B cells and by CD4CTLs drive an exaggerated wound healing response resulting in fibrosis and compromised tissue function.
Authors: Hugues Allard-Chamard; Faisal Alsufyani; Naoki Kaneko; Kelly Xing; Cory Perugino; Vinay S Mahajan; Joseph L Wheat; George S Deepe; James Loyd; Shiv Pillai Journal: J Immunol Date: 2020-12-16 Impact factor: 5.422
Authors: Jiachen Liu; Wei Yin; Lisa S Westerberg; Pamela Lee; Quan Gong; Yan Chen; Lingli Dong; Chaohong Liu Journal: Front Immunol Date: 2021-09-01 Impact factor: 7.561
Authors: Ji Zongfei; Chen Rongyi; Cui Xiaomeng; Ma Lili; Ma Lingying; Kong Xiufang; Dai Xiaomin; Zhang Zhuojun; Chen Huiyong; Sun Ying; Jiang Lindi Journal: Front Immunol Date: 2020-07-08 Impact factor: 7.561