Depletion of Mcpip1 in murine myeloid cells results in intestinal dysbiosis followed by allergic inflammation.

Weronika Szukala, Magdalena Pilarczyk-Zurek, Justyna Folkert, Jerzy Kotlinowski, Joanna Koziel, Jolanta Jura

Biochimica et biophysica acta. Molecular basis of disease 2023 Oct

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MCPIP1 (called also Regnase-1) is a negative regulator of inflammation. Knockout of the Zc3h12a gene, encoding Mcpip1 in cells of myeloid origin (Mcpip1MKO), has a pathological effect on many organs. The aim of this study was to comprehensively analyze pathological changes in the skin caused by Mcpip1 deficiency in phagocytes with an emphasis on its molecular mechanism associated with microbiome dysbiosis. Mcpip1MKO mice exhibited spontaneous wound formation on the skin. On a molecular level, the Th2-type immune response was predominantly characterized by an increase in Il5 and Il13 transcript levels, as well as eosinophil and mast cell infiltration. Irritation by DNFB led to a more severe skin contact allergy in Mcpip1MKO mice. Allergic reactions on the skin were strongly influenced by gut dysbiosis and enhanced systemic dissemination of bacteria. This process was followed by activation of the C/EBP pathway in peripheral macrophages, leading to local changes in the cytokine microenvironment that promoted the Th2 response. A reduced bacterial load inhibited allergic inflammation, indicating the role of intestinal dysbiosis in the development of skin diseases. Our results clearly show that MCPIP1 in phagocytes is an essential negative regulator that controls the gut-skin axis. Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Citation

Weronika Szukala, Magdalena Pilarczyk-Zurek, Justyna Folkert, Jerzy Kotlinowski, Joanna Koziel, Jolanta Jura. Depletion of Mcpip1 in murine myeloid cells results in intestinal dysbiosis followed by allergic inflammation. Biochimica et biophysica acta. Molecular basis of disease. 2023 Oct;1869(7):166764