TNFAIP3 in circulating and parenchymal myeloid lineage critically controls monocytes, monocytes-derived cells and microglia

Background. The intracellular ubiquitin-ending enzyme TNFAIP3 is one of the most potent inhibitor of the pro-inflammatory NF-kB pathway. Single nucleotide polymorphisms in the TNFAIP3 locus have been associated to autoimmune inflammatory disorders, including Multiple Sclerosis (MS). Previously, we reported a TNFAIP3 down-regulated gene expression level in blood and specifically in CD14+ monocytes obtained from treatment naïve MS patients in comparison to healthy controls (HC). Notably, myeloid cells which include monocytes, exert a key role in the neuro-inflammatory pathogenic process of MS.Methods. Here, we evaluated the effect of the specific TNFAIP3 deficiency in myeloid cells including monocytes, monocyte-derived cells (M-MDC) and microglia analyzing the lymphoid organs and central nervous system (CNS) of experimental mice. The TNFAIP3 deletion is induced using conditional knock-out mice for the myeloid lineage. Flow cytometry and histological procedures were applied to evaluate the immune cell population of spleen, lymph nodes and bone marrow and the microglial cell density in CNS, respectively.Results. Here, we found that the deletion of TNFAIP3 in myeloid cells induces a reduced body weight, a decrease in the percentage number of M-MDC and of common monocyte and granulocyte precursor cells. We also reported that the deletion of TNFAIP3 in myeloid cells reports an increased microglial cell density in brain.Conclusions. Collectively, the results suggest that the presence of TNFAIP3 in myeloid cells critically controls the development of M-MDC in lymphoid organ and of microglia in brain.