Papel de las citocinas IL-36 en la regulación de la respuesta inmune en mucosa intestinal
Mucosal innate immunity functions as the rst line of defense against invading pathogens. Members of the IL-1 family are key cytokines upregulated in the in amed mucosa. In ammatory cytokines are regulated by limiting their function and availability through their activation and secretion mechanisms. IL-1 cytokines secretion is affected by the lack of a signal peptide on their sequence, which prevents them from accessing the conventional protein secretion pathway; thus, they use unconventional protein secretion pathways. Here we show in mouse macrophages that LPS/ATP stimulation induces cytokine relocalization to the plasma membrane, and conventional secretion blockade using monensin or Brefeldin A triggers no IL-36\(\gamma\) accumulation within the cell. In silico modeling indicates IL-36\(\gamma\) can pass through both the P2X7R and Gasdermin D pores, and both IL-36\(\gamma\), P2X7R and Gasdermin D mRNA are upregulated in in ammation; further, experimental blockade of these receptors’ limits IL-36\(\gamma\) release. Our results demonstrate that IL-36\(\gamma\) is secreted mainly by an unconventional pathway through membrane pores formed by P2X7R and Gasdermin D.
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