TLR7 agonism accelerates disease in a mouse model of primary Sjögren’s syndrome and drives expansion of T-bet+ B cells
Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by chronic inflammation of exocrine tissue, resulting in loss of tears and saliva. Patients also experience many extra-glandular disease manifestations. Treatment for pSS is palliative, and there are currently no treatme...
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| Format: | Article |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1034336/full |
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| author | Achamaporn Punnanitinont Eileen M. Kasperek Jeremy Kiripolsky Chengsong Zhu Jeffrey C. Miecznikowski Jill M. Kramer |
| author_facet | Achamaporn Punnanitinont Eileen M. Kasperek Jeremy Kiripolsky Chengsong Zhu Jeffrey C. Miecznikowski Jill M. Kramer |
| author_sort | Achamaporn Punnanitinont |
| collection | DOAJ |
| description | Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by chronic inflammation of exocrine tissue, resulting in loss of tears and saliva. Patients also experience many extra-glandular disease manifestations. Treatment for pSS is palliative, and there are currently no treatments available that target disease etiology. Previous studies in our lab demonstrated that MyD88 is crucial for pSS pathogenesis in the NOD.B10Sn-H2b (NOD.B10) pSS mouse model, although the way in which MyD88-dependent pathways become activated in disease remains unknown. Based on its importance in other autoimmune diseases, we hypothesized that TLR7 activation accelerates pSS pathogenesis. We administered the TLR7 agonist Imiquimod (Imq) or sham treatment to pre-disease NOD.B10 females for 6 weeks. Parallel experiments were performed in age and sex-matched C57BL/10 controls. Imq-treated pSS animals exhibited cervical lymphadenopathy, splenomegaly, and expansion of TLR7-expressing B cells. Robust lymphocytic infiltration of exocrine tissues, kidney and lung was observed in pSS mice following treatment with Imq. TLR7 agonism also induced salivary hypofunction in pSS mice, which is a hallmark of disease. Anti-nuclear autoantibodies, including Ro (SSA) and La (SSB) were increased in pSS mice following Imq administration. Cervical lymph nodes from Imq-treated NOD.B10 animals demonstrated an increase in the percentage of activated/memory CD4+ T cells. Finally, T-bet+ B cells were expanded in the spleens of Imq-treated pSS mice. Thus, activation of TLR7 accelerates local and systemic disease and promotes expansion of T-bet-expressing B cells in pSS. |
| first_indexed | 2024-04-11T06:07:48Z |
| format | Article |
| id | doaj.art-8bbe836b94844390a760c8fef30258a3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T06:07:48Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8bbe836b94844390a760c8fef30258a32022-12-22T04:41:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10343361034336TLR7 agonism accelerates disease in a mouse model of primary Sjögren’s syndrome and drives expansion of T-bet+ B cellsAchamaporn Punnanitinont0Eileen M. Kasperek1Jeremy Kiripolsky2Chengsong Zhu3Jeffrey C. Miecznikowski4Jill M. Kramer5Department of Oral Biology, School of Dental Medicine, The University at Buffalo, State University of New York, Buffalo, NY, United StatesDepartment of Oral Biology, School of Dental Medicine, The University at Buffalo, State University of New York, Buffalo, NY, United StatesDepartment of Oral Biology, School of Dental Medicine, The University at Buffalo, State University of New York, Buffalo, NY, United StatesDepartment of Immunology, Microarray & Immune Phenotyping Core Facility, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Biostatistics, School of Public Health and Health Professions, The University at Buffalo, State University of New York, Buffalo, NY, United StatesDepartment of Oral Biology, School of Dental Medicine, The University at Buffalo, State University of New York, Buffalo, NY, United StatesPrimary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by chronic inflammation of exocrine tissue, resulting in loss of tears and saliva. Patients also experience many extra-glandular disease manifestations. Treatment for pSS is palliative, and there are currently no treatments available that target disease etiology. Previous studies in our lab demonstrated that MyD88 is crucial for pSS pathogenesis in the NOD.B10Sn-H2b (NOD.B10) pSS mouse model, although the way in which MyD88-dependent pathways become activated in disease remains unknown. Based on its importance in other autoimmune diseases, we hypothesized that TLR7 activation accelerates pSS pathogenesis. We administered the TLR7 agonist Imiquimod (Imq) or sham treatment to pre-disease NOD.B10 females for 6 weeks. Parallel experiments were performed in age and sex-matched C57BL/10 controls. Imq-treated pSS animals exhibited cervical lymphadenopathy, splenomegaly, and expansion of TLR7-expressing B cells. Robust lymphocytic infiltration of exocrine tissues, kidney and lung was observed in pSS mice following treatment with Imq. TLR7 agonism also induced salivary hypofunction in pSS mice, which is a hallmark of disease. Anti-nuclear autoantibodies, including Ro (SSA) and La (SSB) were increased in pSS mice following Imq administration. Cervical lymph nodes from Imq-treated NOD.B10 animals demonstrated an increase in the percentage of activated/memory CD4+ T cells. Finally, T-bet+ B cells were expanded in the spleens of Imq-treated pSS mice. Thus, activation of TLR7 accelerates local and systemic disease and promotes expansion of T-bet-expressing B cells in pSS.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1034336/fullautoantibodiesNOD.B10autoimmunityage-associated B cellsABCsialadenitis |
| spellingShingle | Achamaporn Punnanitinont Eileen M. Kasperek Jeremy Kiripolsky Chengsong Zhu Jeffrey C. Miecznikowski Jill M. Kramer TLR7 agonism accelerates disease in a mouse model of primary Sjögren’s syndrome and drives expansion of T-bet+ B cells Frontiers in Immunology autoantibodies NOD.B10 autoimmunity age-associated B cells ABC sialadenitis |
| title | TLR7 agonism accelerates disease in a mouse model of primary Sjögren’s syndrome and drives expansion of T-bet+ B cells |
| title_full | TLR7 agonism accelerates disease in a mouse model of primary Sjögren’s syndrome and drives expansion of T-bet+ B cells |
| title_fullStr | TLR7 agonism accelerates disease in a mouse model of primary Sjögren’s syndrome and drives expansion of T-bet+ B cells |
| title_full_unstemmed | TLR7 agonism accelerates disease in a mouse model of primary Sjögren’s syndrome and drives expansion of T-bet+ B cells |
| title_short | TLR7 agonism accelerates disease in a mouse model of primary Sjögren’s syndrome and drives expansion of T-bet+ B cells |
| title_sort | tlr7 agonism accelerates disease in a mouse model of primary sjogren s syndrome and drives expansion of t bet b cells |
| topic | autoantibodies NOD.B10 autoimmunity age-associated B cells ABC sialadenitis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1034336/full |
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