fetching data ...

AB1119 (2024)
REPRESSION OF ID3 AGGRAVATES LUPUS PHENOTYPES IN MURINE MODELS VIA ABERRANT B CELL DIFFERENTIATION
Keywords: Adaptive immunity, Animal Models
Y. Park1, D. S. Kim2, M. L. Cho3, S. K. Kwok1
1Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Division of Rheumatology, Department of Internal Medicine, Seoul, Korea, Rep. of (South Korea)
2The Catholic University of Korea, Department of Biomedicine & Health Sciences, College of Medicine, Seoul, Korea, Rep. of (South Korea)
3The Catholic University of Korea, The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, Seoul, Korea, Rep. of (South Korea)

Background: Id3 is a member of the inhibitor of DNA binding (Id) family which is a helix-loop-helix protein acting as a transcriptional regulator. Previous studies have reported that Id3 plays an important role in development and function of regulatory T cells in lupus. However, its role in B cells remains unclarified.


Objectives: To investigate a role Id3 in B cells and lupus pathogenesis.


Methods: To investigate a role of Id3 in B cells, we generated C57BL/6 mice with a CD19Cre-mediated B cell-specific depletion of Id3 as well as mice (Id3-/-) with conventional knockout of Id3. In these mice, we evaluated presentation of lupus-mimicking phenotypes and changes of immune cell populations. Additionally, we assessed influences of B cell-specific Id3 depletion in lupus-induced mice by R848.


Results: In Id3-/- mice, proportions of effector T cells such as Th1, Th2, and Th17 cells were elevated whereas those of regulatory T cells were lower than in control mice. Furthermore, proportions of plasma cells were significantly elevated in Id3-/- mice. These mice presented with increased inflammation in kidney tissues, resembling lupus nephritis. Elevated proportion of plasma cells was replicated in mice with B cell-specific Id3 depletion. Induction using R848 resulted in exacerbated lupus-like manifestations including increased proteinuria and higher serum immunoglobulin levels in B cell-specific Id3-depleted mice than in control mice. In an in vitro study, CD19+ B cells from Id3-/- mice were more differentiated into plasma cells than those from control mice whereas there were no significant differences in other B cell subsets.


Conclusion: Genetic suppression of Id3 in murine models exacerbated lupus-like phenotypes with aberrant B cell differentiation. These findings may imply a potential role of Id3 in the pathogenesis of lupus.


REFERENCES: NIL.


Acknowledgements: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number: 2022R1I1A1A01068210).


Disclosure of Interests: None declared.

DOI: 10.1136/annrheumdis-2024-eular.3801
Keywords: Adaptive immunity, Animal Models
Citation: , volume 83, supplement 1, year 2024, page 1891
Session: Systemic lupus erythematosus (Publication Only)