Pathogenic T Cells in Celiac Disease Change Phenotype on Gluten Challenge: Implications for T-Cell-Directed Therapies
Asbjørn Christophersen,Asbjørn Christophersen,Stephanie Zühlke,Eivind G. Lund,Omri Snir,Shiva Dahal-Koirala,Louise Fremgaard Risnes,Louise Fremgaard Risnes,Jørgen Jahnsen,Jørgen Jahnsen,Knut E.A. Lundin,Knut E.A. Lundin,Ludvig M. Sollid,Ludvig M. Sollid +13 more
TLDR
In this article, a 3-day gluten challenge was used to study the phenotype of gluten-specific CD4+ T cells in patients with celiac disease (CeD) and other autoimmune conditions.Abstract:
Gluten-specific CD4+ T cells being drivers of celiac disease (CeD) are obvious targets for immunotherapy. Little is known about how cell markers harnessed for T-cell-directed therapy can change with time and upon activation in CeD and other autoimmune conditions. In-depth characterization of gluten-specific CD4+ T cells and CeD-associated (CD38+ and CD103+ ) CD8+ and γδ+ T cells in blood of treated CeD patients undergoing a 3 day gluten challenge is reported. The phenotypic profile of gluten-specific cells changes profoundly with gluten exposure and the cells adopt the profile of gluten-specific cells in untreated disease (CD147+ , CD70+ , programmed cell death protein 1 (PD-1)+ , inducible T-cell costimulator (ICOS)+ , CD28+ , CD95+ , CD38+ , and CD161+ ), yet with some markers being unique for day 6 cells (C-X-C chemokine receptor type 6 (CXCR6), CD132, and CD147) and with integrin α4β7, C-C motif chemokine receptor 9 (CCR9), and CXCR3 being expressed stably at baseline and day 6. Among gluten-specific CD4+ T cells, 52% are CXCR5+ at baseline, perhaps indicative of germinal-center reactions, while on day 6 all are CXCR5- . Strikingly, the phenotypic profile of gluten-specific CD4+ T cells on day 6 largely overlaps with that of CeD-associated (CD38+ and CD103+ ) CD8+ and γδ+ T cells. The antigen-induced shift in phenotype of CD4+ T cells being shared with other disease-associated T cells is relevant for development of T-cell-directed therapies.read more
Citations
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Journal ArticleDOI
Immunopathogenesis and environmental triggers in coeliac disease
TL;DR: Demonstration that lymphomas complicating CD arise from IEL that have acquired gain-of-function JAK1 or STAT3 mutations stresses the key role of this pathway and explains how gluten-driven chronic inflammation may promote this rare but most severe complication.
Journal ArticleDOI
The Immunobiology and Pathogenesis of Celiac Disease.
Rasmus Iversen,Ludvig M. Sollid +1 more
TL;DR: Current understanding of the immunobiology of celiac disease is presented, with mechanistic insights into how the disease-predisposing HLA-DQ molecules, via presentation of posttranslationally modified gluten peptides, are connected to the generation of these autoantibodies.
Journal ArticleDOI
Phenotype‐Based Isolation of Antigen‐Specific CD4+ T Cells in Autoimmunity: A Study of Celiac Disease
Asbjørn Christophersen,Shiva Dahal-Koirala,Marketa Chlubnova,Jørgen Jahnsen,Knut E.A. Lundin,Ludvig M. Sollid +5 more
TL;DR: The feasibility to isolate antigen‐specific CD4+ T cells by the sole use of phenotypic markers in CeD outlines a potential avenue for characterizing disease‐driving CD4 + T cells in autoimmune conditions.
Journal ArticleDOI
Emergence of an adaptive immune paradigm to explain celiac disease: a perspective on new evidence and implications for future interventions and diagnosis.
TL;DR: The role and clinical effects of CD4+ T cells directed against deamidated gluten in the context of an "adaptive immune paradigm" are reviewed in this paper, where alternative hypotheses of gluten toxicity are discussed and contrasted.
Journal ArticleDOI
Emergence of an adaptive immune paradigm to explain celiac disease: a perspective on new evidence and implications for future interventions and diagnosis
TL;DR: The role and clinical effects of CD4+ T cells directed against deamidated gluten in the context of an "adaptive immune paradigm" are reviewed in this article , where the implications of the adaptive immune paradigm for future strategies to prevent, diagnose, and treat celiac disease are outlined.
References
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Journal ArticleDOI
Circulating CD103 + γδ and CD8 + T cells are clonally shared with tissue-resident intraepithelial lymphocytes in celiac disease
Louise Fremgaard Risnes,Louise Fremgaard Risnes,Linn M Eggesbø,Stephanie Zühlke,Stephanie Zühlke,Shiva Dahal-Koirala,Ralf Stefan Neumann,Knut E.A. Lundin,Knut E.A. Lundin,Asbjørn Christophersen,Ludvig M. Sollid,Ludvig M. Sollid +11 more
TL;DR: In this paper, the authors examined the clonal relationship between cells of blood and gut during gluten exposure and found extensive sharing between blood and colon TCRs even prior to a gluten challenge.
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