Type 2 transglutaminase (TG2) has an important pathogenic role in celiac disease 
(CD), an inflammatory intestinal disease that is caused by the ingestion of 
gluten-containing cereals. Indeed, TG2 deamidates specific gliadin peptides, 
thus enhancing their immunogenicity. Moreover, the transamidating activity seems 
to provoke an autoimmune response, where TG2 is the main autoantigen. Many 
studies have highlighted a possible pathogenetic role of anti-TG2 antibodies, 
because they modulate TG2 enzymatic activity and they can interact with 
cell-surface TG2, triggering a wide range of intracellular responses. 
Autoantibodies also alter the uptake of the alpha-gliadin peptide 31-43 
(p31-43), responsible of the innate immune response in CD, thus partially 
protecting cells from p31-43 damaging effects in an intestinal cell line. Here, 
we investigated whether anti-TG2 antibodies protect cells from p31-43-induced 
damage in a CD model consisting of primary dermal fibroblasts. We found that the 
antibodies specifically reduced the uptake of p31-43 by fibroblasts derived from 
healthy subjects but not in those derived from CD patients. Analyses of TG2 
expression and enzymatic activity did not reveal any significant difference 
between fibroblasts from healthy and celiac subjects, suggesting that other 
features related to TG2 may be responsible of such different behaviors, e.g., 
trafficking or subcellular distribution. Our findings are in line with the 
concept that a "celiac cellular phenotype" exists and that TG2 may contribute to 
this phenotype. Moreover, they suggest that the autoimmune response to TG2, 
which alone may damage the celiac mucosa, also fails in its protective role in 
celiac cells.