088 | Investigating the role of Hsp60 in the pathophysiology of celiac disease

Giusy Vultaggio¹, Giuseppe Vergilio^1|2, Letizia Paladino³, Rosario Barone¹, Francesca Rappa¹ | ¹Department of Biomedicine, Neuroscience and Advanced Diagnostics BIND, University of Palermo, Italy; ²Department of Neurosurgery, National Relevance and High Specialization Hospital Trust ARNAS Civico, Palermo, Italy; ³Department of Theoretical and Applied Sciences, eCampus University, Novedrate [CO], Italy.

Celiac disease (CD) is a chronic immune-mediated disorder of the small intestine triggered by the ingestion of gluten in genetically predisposed individuals carrying the HLA-DQ2 and/or HLA-DQ8 haplotypes¹. It is characterized by CD4⁺ T cell–driven inflammation with release of pro-inflammatory cytokines (IFN-γ and IL-15¹), villous atrophy, impaired intestinal barrier function, and modulation by environmental factors such as infections, gut microbiota alterations, and coexisting autoimmune disorders [1]. In addition to the adaptive immune response induced by gluten, increasing evidence supports a role for innate immunity and cellular stress pathways in sustaining chronic intestinal inflammation in CD². Heat shock proteins (HSPs), particularly Hsp60, may act as molecular danger signals in inflammatory conditions and, when released extracellularly, can activate Toll-like receptor 4 (TLR4)–dependent NF-κB signaling, thereby promoting the transcription of pro-inflammatory mediators, immune cell recruitment, epithelial stress, and intestinal barrier dysfunction [2,3]. This study aimed to characterize the expression and potential role of Hsp60 in CD and its involvement in innate immunity activation. Duodenal biopsies from healthy controls and CD patients at different disease stages were analyzed by immunohistochemistry and immunofluorescence. Hsp60 expression increased in a stage-dependent manner from Marsh 0 to Marsh 3c, paralleling the increase in CD68-positive cells and showed marked co-localization between Hsp60 and CD68. TLR4 expression was also upregulated at all stages of the disease and strongly co-localized with Hsp60. Together, these findings suggest that Hsp60 may link epithelial stress to innate immune activation during CD progression, supporting a role for the Hsp60–TLR4 axis in mucosal inflammation and identifying Hsp60 as a potential therapeutic target.