Endocrine Abstracts

JOINT1461

Introduction: Hashimotós thyroiditis (HT) is an autoimmune thyroid disorder (AITD) that result from the dysregulation of the immune system tolerance, leading to an immune response against self-thyroid antigens. Thyroid follicular cells (TFCs) display a key role in antigen presentation due to the acquisition of the major histocompatibility complex II (MHC-II) in a proinflammatory environment. CD74 is the invariant chain of MHC-II and collaborates in the endosomal trafficking and the assembly of this complex. The antigen presentation process requires costimulatory signals to reinforce the contact between the antigen presenting cells and the receptor immune cell. Hereby, CD80 and CD86 display a key role as correceptors of MHC-II. Regarding the contribution of TFCs to HT pathogenesis, we evaluated the role of CD74 in TFCs from HT patients.

Methodology: We analyzed CD74 and CD80 expression in thyroid tissue from controls and HT patients by spatial transcriptomics and immunofluorescences (IF). We measured the expression of these markers in a human thyroid cell line in vitro model with the stimulation of proinflammatory cytokines (IFN-γ and TNF-α) by western blot (WB), IF and flow citometry. Furthermore, we established coculture assays of thyrocytes with a T lymphocyte cell line (Jurkat E6.1) in combination with a CD74 inhibitor (milatuzumab) and we evaluated the levels of CD69 and CD25 as T cell activation markers.

Results: We observed a significant increase of CD74 expression in tissue from HT patients compared to controls. Interestingly, CD74 staining was associated to CD80 only in TFCs from HT patients. In the in vitro model, IFN-γ and TNF-α increased the expression of CD74, CD80 and MHC-II. The use of milatuzumab could partially revert the increase of antigen presentation markers in thyroid cells and reduced the activation of T cells, suggesting a role of CD74 in antigen presentation and T cell activation.

Conclusions: Our data suggests a role of CD74 in HT pathogenesis. The use of milatuzumab as a CD74 inhibitor may represent a potential therapy to ameliorate immune cell reactivity.