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Abstract Number: 0998

Differential Roles of TNFRI and TNFRII in the Morphology of Secondary Lymphoid Organs

Kim Jeucken1, Jan Piet van Hamburg1 and Sander Tas2, 1Amsterdam Rheumatology and Immunology Center (ARC), Department of Rheumatology and Clinical Immunology, Department of Experimental Immunology and Amsterdam Infection and Immunity Institute, Amsterdam UMC; location AMC, University of Amsterdam, Netherlands, Amsterdam, Netherlands, 2Amsterdam Rheumatology and Immunology Center (ARC), Department of Rheumatology and Clinical Immunology, Department of Experimental Immunology and Amsterdam Infection and Immunity Institute, Amsterdam UMC; location AMC, University of Amsterdam, Netherlands, Utrecht, Netherlands

Meeting: ACR Convergence 2020

Keywords: B-Lymphocyte, Mouse, spondyloarthritis, T-Lymphocyte, Tumor necrosis factor (TNF)

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Session Information

Date: Sunday, November 8, 2020

Session Title: B Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster

Session Type: Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Tumour necrosis factor (TNF) induced signaling events are important in lymphoid organ development and function, both in health and in immune-mediated inflammatory diseases such as arthritis. Important receptors involved in this process include TNF receptors (R) I and II that exert distinct functions. Mice overexpressing transmembrane ™TNF develop various features of chronic inflammation, including arthritis, that are mediated via TNFRI and/or TNFRII. In this study we investigated the contribution of TNFRI and TNFRII in spleen and peripheral lymph node (PLN) morphology in transgenic mice overexpressing tmTNF (tmTNF-tg).

Methods: Spleen and PLN were collected from wild type (wt) and heterozygous tmTNF-tg mice, with were either on a normal or TNFRI or TNFRII deficient background. Spleens were stained by immunofluorescence for B and T cell markers, imaged by confocal microscopy and analyzed using FIJI software. PLN were used for whole mount tissue staining for B and T cell markers, cleared, 3D imaged by light sheet microscopy and analyzed using Imaris software.

Results: TmTNF-tg mice exhibited an altered spleen morphology characterized by smaller follicles (tmTNF-tg 69.73 ± 72.25 µm2; wt 139.3 ± 71.36 µm2), and a reduced proportion of follicle T cell area (tmTNF-tg 15.22 ± 9.69%; wt 26.60 ± 10.46%). Spleen morphology of TNFRI-/- and TNFRII-/- mice was similar to wt mice. TmTNF-tg x TNFRI-/- exhibited a normal spleen architecture (follicle size: 239.2 ± 250.5 µm2; T cell area: 29.92 ± 11.46%). In contrast, spleen follicles of tmTNF-tg x TNFRII-/- mice had T cell areas (17.31 ± 8.88%) comparable to tmTNF-tg mice. PLNs of tmTNF-tg mice were increased in size (tmTNF-tg 3.74 ± 1.31 mm3; wt 2.41 ± 0.60 mm3), also in combination with deficiency of TNFRI (3.98 ± 2.07 mm3) or TNFRII (4.01 ± 1.96 mm3). TmTNF-tg PLNs had an increase in absolute B cell volume (tmTNF-tg 0.86 ± 0.33 mm3; wt 0.51 ± 0.07 mm3), but no change in B cell area as proportion of total PLN volume. The increased B cell volume was critically dependent on TNFRII. Interestingly, TNFRI deficiency caused profound alterations B cell area morphology that appeared as one peripheral layer of B cells covering a central T cell area rather than properly developed follicles.

Conclusion: This study demonstrates that overexpression of tmTNF leads to an aberrant spleen architecture, characterized by smaller follicles and reduced central T cell areas, which is critically dependent on TNFRI. In addition, overexpression of tmTNF results in enlarged PLN and increased total B cell volume, which is dependent on TNFRII, whereas TNFRI is more important in the proper organization of B cell follicles. Overall, this study employing different state-of-the-art (3D) imaging techniques highlights the importance of tmTNF-TNFR-induced signaling events in secondary lymphoid organ morphology and function, and reveals distinct roles for TNFRI and II. Advancing our knowledge in this field might provide a better understanding of the pathophysiology of TNF-associated diseases such as arthritis, which may be important to develop new or improved treatment strategies.


Disclosure: K. Jeucken, None; J. van Hamburg, None; S. Tas, None.

To cite this abstract in AMA style:

Jeucken K, van Hamburg J, Tas S. Differential Roles of TNFRI and TNFRII in the Morphology of Secondary Lymphoid Organs [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/differential-roles-of-tnfri-and-tnfrii-in-the-morphology-of-secondary-lymphoid-organs/. Accessed January 27, 2021.
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