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m6A modification as a potential therapeutic target for autoimmune diseases

N6-methyladenosine (m6A) is the most extensive studied RNA modification across various species, and the important effect of m6A modification in immune system has been revealed in distinct contexts, including mRNA metabolism, cell differentiation, proliferation and response to stimulation.

Danielle ellisHua bing liImmune system

m6A mRNA modification potentiates Th17 functions to inflame autoimmunity

m6A mRNA modification potentiates Th17 functions to inflame autoimmunity
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Xuefei wangHua bing liScience china life sciencesScience chinaScience china pressScience china life

m6A mRNA modification potentiates Th17 functi

In a paper recently published on Science CHINA life sciences, scientists found that ablation of m6A methyltransferase METTL3 caused serious disruption of Th17 cell differentiation. Lineage specific deletion of METTL3 in Th17 cells gave rise to less Th17 cells infiltration into CNS, and significantly suppressed the development of neuroinflammation. These findings uncovered the indispensable role of METTL3 mediated m6A modification in Th17 cell subset and its involvement in autoimmune disease.

Hua bing liScience china life sciencesChina life

Pooled CRISPR screening identifies m6A as a positive regulator of macrophage activation

Cd86), were down-regulated in Mettl3-deficient cells (Fig. 1G), suggesting that METTL3 has a critical function in controlling the innate immune response of Raw 264.7 macrophages. To further confirm the biological role of the m 6A modification in macrophages, Mettl3 conditional KO (CKO) mice were generated by crossing Mettl3 flox/flox mice with mice expressing Cre recombinase under the control of lysozyme 2 promoter ( Lyzm-Cre). We have documented the loss of both the METTL3 protein and the overall m 6A modification in bone marrow–derived macrophages (BMDMs) from Mettl3 flox/flox; Lyzm-Cre mice (fig. S1I). No differences in the frequency of major immune cell populations were observed between

United statesAgilent bioanalyzerAmersham hybondMerck milliporeHua bing liLipofectamine rnaimax invitrogenShanghai jiao tong university school of medicineNational centerNational natural science foundation of chinaQ zou shanghai institute of immunologyZai lab ltdLibrary prep human mouse rat illuminaYale university school of medicineTechnology committeeGe healthcareNational key rd program of china