Faculty Opinions recommendation of Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis.

2005 ◽  
Author(s):  
Ken Smith
Keyword(s):  
B Cells ◽  
Autoimmune Arthritis

scholarly journals Antigen-Specific B Cells Are Required as APCs and Autoantibody-Producing Cells for Induction of Severe Autoimmune Arthritis

2005 ◽  
Vol 174 (6) ◽  
pp. 3781-3788 ◽  
Author(s):  
Shannon K. O’Neill ◽  
Mark J. Shlomchik ◽  
Tibor T. Glant ◽  
Yanxia Cao ◽  
Paul D. Doodes ◽  
...  
Keyword(s):  
B Cells ◽  
Autoimmune Arthritis

scholarly journals Targeting the CD40-CD154 Signaling Pathway for Treatment of Autoimmune Arthritis

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 927 ◽  
Author(s):  
Jenn-Haung Lai ◽  
Shue-Fen Luo ◽  
Ling-Jun Ho
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cellular Proliferation ◽  
Autoimmune Arthritis ◽  
Therapeutic Success ◽  
Immune Effector ◽  
Cell Functions ◽  
Therapeutic Benefits

Full activation of T lymphocytes requires signals from both T cell receptors and costimulatory molecules. In addition to CD28, several T cell molecules could deliver costimulatory signals, including CD154, which primarily interacts with CD40 on B-cells. CD40 is a critical molecule regulating several B-cell functions, such as antibody production, germinal center formation and cellular proliferation. Upregulated expression of CD40 and CD154 occurs in immune effector cells and non-immune cells in different autoimmune diseases. In addition, therapeutic benefits have been observed by blocking the CD40-CD154 interaction in animals with collagen-induced arthritis. Given the therapeutic success of the biologics abatacept, which blocks CD28 costimulation, and rituximab, which deletes B cells in the treatment of autoimmune arthritis, the inhibition of the CD40-CD154 axis has two advantages, namely, attenuating CD154-mediated T cell costimulation and suppressing CD40-mediated B-cell stimulation. Furthermore, blockade of the CD40-CD154 interaction drives the conversion of CD4+ T cells to regulatory T cells that mediate immunosuppression. Currently, several biological products targeting the CD40-CD154 axis have been developed and are undergoing early phase clinical trials with encouraging success in several autoimmune disorders, including autoimmune arthritis. This review addresses the roles of the CD40-CD154 axis in the pathogenesis of autoimmune arthritis and its potential as a therapeutic target.

Treatment of IL-21R-Fc control autoimmune arthritis via suppression of STAT3 signal pathway mediated regulation of the Th17/Treg balance and plasma B cells

2015 ◽  
Vol 163 (2) ◽  
pp. 143-150 ◽  
Author(s):  
Jun-Geol Ryu ◽  
Jennifer Lee ◽  
Eun-Kyung Kim ◽  
Hyeon-beom Seo ◽  
Jin-Sil Park ◽  
...  
Keyword(s):  
B Cells ◽  
Signal Pathway ◽  
Autoimmune Arthritis

scholarly journals Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca2+ Influx in Nkx2-3 Knock-out Mice

2020 ◽  
Vol 21 (17) ◽  
pp. 6162
Author(s):  
Esam Khanfar ◽  
Katalin Olasz ◽  
Fanni Gábris ◽  
Erzsébet Gajdócsi ◽  
Bálint Botz ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Clinical Picture ◽  
Cell Activation ◽  
Cell Receptor ◽  
Histological Structure ◽  
Autoimmune Arthritis ◽  
B Cell Activation ◽  
Knock Out ◽  
Radiological Changes

B cells play a crucial role in the pathogenesis of rheumatoid arthritis. In Nkx2-3-deficient mice (Nkx2-3−/−) the spleen’s histological structure is fundamentally changed; therefore, B cell homeostasis is seriously disturbed. Based on this, we were curious, whether autoimmune arthritis could be induced in Nkx2-3−/− mice and how B cell activation and function were affected. We induced arthritis with immunization of recombinant human proteoglycan aggrecan G1 domain in Nkx2-3−/− and control BALB/c mice. We followed the clinical picture, characterized the radiological changes, the immune response, and intracellular Ca2+ signaling of B cells. Incidence of the autoimmune arthritis was lower, and the disease severity was milder in Nkx2-3−/− mice than in control BALB/c mice. The radiological changes were in line with the clinical picture. In Nkx2-3−/− mice, we measured decreased antigen-induced proliferation and cytokine production in spleen cell cultures; in the sera, we found less anti-CCP-IgG2a, IL-17 and IFNγ, but more IL-1β, IL-4 and IL-6. B cells isolated from the lymph nodes of Nkx2-3−/− mice showed decreased intracellular Ca2+ signaling compared to those isolated from BALB/c mice. Our findings show that the transcription factor Nkx2-3 might regulate the development of autoimmune arthritis most likely through modifying B cell activation.

Deficiency of IL-1 receptor antagonist suppresses IL-10-producing B cells in autoimmune arthritis in an IL-17/Th17-dependent manner

2018 ◽  
Vol 199 ◽  
pp. 44-52 ◽  
Author(s):  
Jin-Sil Park ◽  
Na-Rae Kim ◽  
Mi-Ae Lim ◽  
Sung-Min Kim ◽  
Sun-Hee Hwang ◽  
...  
Keyword(s):  
B Cells ◽  
Receptor Antagonist ◽  
Autoimmune Arthritis ◽  
Dependent Manner

scholarly journals Artesunate Abolishes Germinal Center B Cells and Inhibits Autoimmune Arthritis

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e104762 ◽  
Author(s):  
Lifei Hou ◽  
Katharine E. Block ◽  
Haochu Huang
Keyword(s):  
B Cells ◽  
Germinal Center ◽  
Autoimmune Arthritis ◽  
Germinal Center B Cells

scholarly journals Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis

2015 ◽  
Vol 12 (4) ◽  
pp. 493-504 ◽  
Author(s):  
Anna-Karin E Palm ◽  
Heike C Friedrich ◽  
Anja Mezger ◽  
Maya Salomonsson ◽  
Linda K Myers ◽  
...  
Keyword(s):  
B Cells ◽  
Marginal Zone ◽  
Autoimmune Arthritis ◽  
Marginal Zone B Cells

scholarly journals B-Cell-Targeted 3DNA Nanotherapy Against Indoleamine 2,3-Dioxygenase 2 (IDO2) Ameliorates Autoimmune Arthritis in a Preclinical Model

2020 ◽  
Vol 13 ◽  
pp. 2632010X2095181
Author(s):  
Lauren MF Merlo ◽  
Jessica Bowers ◽  
Tony Stefanoni ◽  
Robert Getts ◽  
Laura Mandik-Nayak
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Types ◽  
Preclinical Model ◽  
Autoimmune Arthritis ◽  
Specific Cell ◽  
Dna Nanostructures ◽  
Intracellular Protein ◽  
Indoleamine 2,3 Dioxygenase ◽  
A Cell

The tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase 2 (IDO2) has been identified as an immunomodulatory agent promoting autoimmunity in preclinical models. As such, finding ways to target the expression of IDO2 in B cells promises a new avenue for therapy for debilitating autoimmune disorders such as rheumatoid arthritis. IDO2, like many drivers of disease, is an intracellular protein expressed in a range of cells, and thus therapeutic inhibition of IDO2 requires a mechanism for targeting this intracellular protein in specific cell types. DNA nanostructures are a promising novel way of delivering small molecule drugs, antibodies, or siRNAs to the cytoplasm of a cell. These soluble, branched structures can carry cell-specific targeting moieties along with their therapeutic deliverable. Here, we examined a 3DNA nanocarrier specifically targeted to B cells with an anti-CD19 antibody. We find that this 3DNA is successfully delivered to and internalized in B cells. To test whether these nanostructures can deliver an efficacious therapeutic dose to alter autoimmune responses, a modified anti-IDO2 siRNA was attached to B-cell-directed 3DNA nanocarriers and tested in an established preclinical model of autoimmune arthritis, KRN.g7. The anti-IDO2 3DNA formulation ameliorates arthritis in this system, delaying the onset of joint swelling and reducing total arthritis severity. As such, a 3DNA nanocarrier system shows promise for delivery of targeted, specific, low-dose therapy for autoimmune disease.

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