About this Research Topic
The tissue-restricted distribution of the non-classical HLA class I molecule HLA-G, the low polymorphism in the coding region, the fact that HLA-G primary transcript is alternatively spliced in seven isoforms, and the inhibitory action on immune cells, constitute four hallmarks of HLA-G, which set it apart from other HLA class I molecules. Although the HLA-G locus is of low polymorphism, variants in both its promoter and 3’ un-translated region (UTR) regulate its expression.
In healthy conditions, a basal level of HLA-G gene transcription is observed in most cells and tissues; however, translation into HLA-G protein is restricted to trophoblasts in the placenta where it participates in the tolerance at the fetal-maternal interface. HLA-G is also expressed by thymic epitelial, cornea, mesenchymal stem cells (MSCs), nail matrix, pancreatic beta cells, erythroid and endothelial precursors.
HLA-G can be neo-expressed in adult tissues in pathological conditions, and its expression has been documented autoimmune disorders, viral infections, and especially cancer. In the latter settings de novo HLA-G expression is associated with the capability of solid tumor cells to evade the immune control.
In the last decade it has become evident that HLA-G expression on T cells and antigen-presenting cells confers them tolerogenic properties. This Research Topic will focus on i) summarizing clinical and immunological evidence on the significance of HLA-G expression for beneficial tolerance or detrimental immune escape, ii) gathering new insights into the mechanisms governing the expression of HLA-G in healthy and pathological conditions, and iii) examining the mechanisms underlying HLA-G mediated tolerance, in order to broader the comprehension of the tolerogenic role mediated by HLA-G and to ultimately advance the definition of novel therapeutic strategies to promote or inhibit HLA-G-mediated tolerance.
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