Early Covert Appearance of Marginal Zone B Cells in Salivary Glands of Sjögren′s Syndrome-Susceptible Mice: Initiators of Subsequent Overt Clinical Disease
| Autor: | Cuong Q. Nguyen, Julian L. Ambrus, Ammon B. Peck |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Exocrine gland T-Lymphocytes medicine.disease_cause Salivary Glands Autoimmunity lcsh:Chemistry Mice 0302 clinical medicine Cell Movement Mice Inbred NOD Sphingosine C57BL/6.NOD-Aec1Aec2 mice Receptor Notch2 sphingosine-1-phosphate receptor (S1PR) RNA transcriptome microarrays lcsh:QH301-705.5 Spectroscopy B-Lymphocytes Salivary gland General Medicine Marginal zone Computer Science Applications B cell receptor (BCR) sphingosine-1-phosphate (S1P) sphingosine-1-phosphate receptor (S1PR) RNA transcriptome microarrays Sjogren's Syndrome medicine.anatomical_structure marginal zone B (MZB) cells marginal zones (MZ) Receptors Antigen B-Cell Biology Article Catalysis Inorganic Chemistry 03 medical and health sciences Immune system Antigen medicine Animals Physical and Theoretical Chemistry CXCL13 Sphingosine-1-Phosphate Receptors Molecular Biology B cell Autoantibodies 030203 arthritis & rheumatology Notch2 Gene Expression Profiling Organic Chemistry B cell receptor (BCR) Chemokine CXCL13 Mice Inbred C57BL Sjögren´s syndrome Disease Models Animal 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Sjögren’s syndrome Immunology sphingosine-1-phosphate (S1P) Lysophospholipids Transcriptome marginal zones (MZ) marginal zone B (MZB) cells |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 1919, p 1919 (2021) International Journal of Molecular Sciences Volume 22 Issue 4 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | The C57BL/6.NOD-Aec1Aec2 mouse model has been extensively studied to define the underlying cellular and molecular bioprocesses critical in the onset of primary Sjögren’s Syndrome (pSS), a human systemic autoimmune disease characterized clinically as the loss of lacrimal and salivary gland functions leading to dry eye and dry mouth pathologies. This mouse model, together with several gene knockout mouse models of SS, has indicated that B lymphocytes, especially marginal zone B (MZB) cells, are necessary for development and onset of clinical manifestations despite the fact that destruction of the lacrimal and salivary gland cells involves a classical T cell-mediated autoimmune response. Because migrations and functions of MZB cells are difficult to study in vivo, we have carried out ex vivo investigations that use temporal global RNA transcriptomic analyses to profile autoimmunity as it develops within the salivary glands of C57BL/6.NOD-Aec1Aec2 mice. Temporal profiles indicate the appearance of Notch2-positive cells within the salivary glands of these SS-susceptible mice concomitant with the early-phase appearance of lymphocytic foci (LF). Data presented here identify cellular bioprocesses occurring during early immune cell migrations into the salivary glands and suggest MZB cells are recruited to the exocrine glands by the upregulated Cxcl13 chemokine where they recognize complement (C’)-decorated antigens via their sphingosine-1-phosphate (S1P) and B cell (BC) receptors. Based on known MZB cell behavior and mobility, we propose that MZB cells activated in the salivary glands migrate to splenic follicular zones to present antigens to follicular macrophages and dendritic cells that, in turn, promote a subsequent systemic cell-mediated and autoantibody-mediated autoimmune T cell response that targets exocrine gland cells and functions. Overall, this study uses the power of transcriptomic analyses to provide greater insight into several molecular events defining cellular bioprocesses underlying SS that can be modelled and more thoroughly studied at the cellular level. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|