Conventional dendritic cells are more activated in the hyperplastic Thymus of myasthenia gravis patients

Abstract

Introduction: Dendritic cells (DCs) are crucial to form ectopic germinal centers (GCs) in the hyperplastic thymus (HT), which are typically found in anti-acetylcholine receptor autoantibody-positive myasthenia gravis (MG) patients. However, the characteristics of such DCs in the HT and their roles in thymic hyperplasia formation remain unclear.

Methods: We collected thymic tissue from MG patients and patients who underwent cardiac surgery. The tissues were cut into sections for immunohistochemistry and immunofluorescence or digested into a single cell suspension for flow cytometry.

Results: In addition to formation of ectopic GCs, we found that the proportion of the medulla in the thymic parenchyma was higher than that in the cortex (area_cortex/area_medulla, 1.279 vs. 0.6576) in the HT of MG patients. The density of conventional dendritic cells (cDCs) in the HT was 131 ± 64.36 per mm², whereas in normal thymic tissue, the density was 59.17 ± 22.54 per mm². The more abundant cDCs expressed co-stimulatory molecules (CD80 and CD86) strongly. Moreover, the more abundant subset was mainly CD141+ DCs (cDC1s), accounting for an increase from 15% to 29%. However, these increased cDC1s appeared to be unrelated to Hassall's corpuscles and ectopic GCs.

Conclusion: Thymic hyperplasia in MG patients is manifested as an increase in the proportion of the thymic medulla accompanied by increases in the density and functional activation as well as changes in the subset composition of cDCs.

Keywords: Conventional dendritic cells; Ectopic germinal center; Myasthenia gravis; Subsets; Thymic hyperplasia.