PhD Scientific Days 2025

Molecular Medicine V.

The role of a C-type lectin receptor in immune complex-mediated inflammation

Name of the presenter

Balogh Lili

Institute/workplace of the presenter

Department of Physiology, Semmelweis University

Authors

Lili Balogh¹, Eszter Káposztás¹, Silvia Hayer², Stephan Blüml², Attila Mócsai¹, Tamás Németh¹

1: Department of Physiology, Semmelweis University, Budapest, Hungary
2: Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria

Text of the abstract

Introduction: Gene polymorphisms of the C-type lectin receptor Dectin-2 have been associated with an autoimmune disease, while we have found that Dectin-2 was heavily upregulated in immune complex-stimulated mouse neutrophils under in vitro conditions.
Aims: These data prompted us to test the role of Dectin-2 in immune complex-mediated neutrophil cell responses and in a neutrophil-dependent autoimmune skin disease, in experimental epidermolysis bullosa acquisita (EBA).
Methods: We used wild type and Dectin-2 knockout (Dectin-2‒/‒) mice. Freshly isolated mouse neutrophils were activated by immune complexes. Superoxide release was measured by a cytochrome c reduction test, while cytokine levels were detected by ELISA. Neutrophil migration was tested in the in vitro Transwell assay. Experimental dermatitis was triggered by subcutaneous injections of anti-collagen VII (anti-CVII) antibodies. Disease progression was followed by clinical scoring and ear thickness measurement. Immune cell accumulation in the ears was detected by flow cytometry, while local chemokine levels were measured by ELISA.
Results: Immune complex-activated Dectin-2‒/‒ neutrophils showed significantly decreased superoxide and cytokine release in contrast to wild type cells. Furthermore, Dectin-2‒/‒ mice were almost completely protected from the development of experimental dermatitis compared to wild type animals (while the antibody-deposition in the skin and the serum anti-CVII antibody levels did not differ in the two genotypes). In line with these findings, the in vivo neutrophil recruitment and the tested chemokine levels were also massively reduced in the ears of Dectin-2‒/‒ mice. However, the migration of neutrophils seemed to be independent of the presence of Dectin-2.
Conclusions: Our results indicate that Dectin-2 has an essential role in the development of autoimmune dermatitis, which is probably due to the importance of this C-type lectin receptor in immune complex-mediated neutrophil functions. Our findings help us to better understand the pathomechanism of Fc receptor-mediated autoimmune processes and Dectin-2 may serve as a potential therapeutic target in immune complex-triggered autoimmune diaseases in the future.
Funding: This work was funded by the Hungarian National Research, Development and Innovation Office. L.B. is a recipient of an SE 250+ Excellence PhD Scholarship.