Nkx2-3—A Slippery Slope From Development Through Inflammation Toward Hematopoietic Malignancies

Abstract

The development of peripheral lymphoid tissues from the mesoderm is the result of a complex convergence combining lymphohematopoietic differentiation with the local specification of nonhematopoietic mesenchymal components. Although the various transcriptional regulators with fate-determining effects in diversifying the mobile leukocyte subsets have been thoroughly studied and identified, the tissue-specific determinants promoting the regional differentiation of resident mesenchyme are less understood. Of these factors, various members of the NK-class Nkx paralogues have emerged as key regulators for the organogenesis of spleen and mucosal lymphoid tissues, and recent data have also indicated their involvement in various pathological events, including gut inflammation and hematopoietic malignancies. Here, we summarize available data on the roles of Nkx2-3 in lymphoid tissue development and discuss its possible value as a developmental marker and disease-associated pathogenic trait.

Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca2+ Influx in Nkx2-3 Knock-out Mice

“…Nirenberg-Kim (NK) 2 homeobox 3 (Nkx2-3) is a homeodomain transcription factor, which is essential for the normal development of the spleen, Peyer’s patches and small intestine [ 14 , 15 , 16 , 17 ]. Along with its role in the development of intestinal lymphoid tissues.…”

“…Along with its role in the development of intestinal lymphoid tissues. Nkx2-3 is crucial for the expression and regulation of the mucosal addressin cell adhesion molecule-1 (MADCAM-1) on the spleen sinus lining cells and on high endothelial venules of the mesenteric lymph nodes and Peyer’s patches [ 17 , 18 , 19 , 20 ]. Nkx2-3 has an important role in spleen organization and function, since it controls the correct micro-environment for B cell maturation and T-cell-dependent (TD) immune reaction [ 14 , 21 ].…”

Identification of A Novel Six Autophagy-Related Genes Signature for The Prognostic and A miRNA-Related Autophagy Predictor for Anti-PD-1 Therapy Responses in Prostate Cancer

“…NKX2-3 may also be classi ed as biomarker to predict the effects of primary advanced colorectal cancer patients who will undergo FOLFOX4 [66]. NKX2-3 has been studied not only in solid malignancies, but also in hematopoietic malignancies [67]. Therefore, it is very valuable to further study NKX2-3 in both solid malignancies and hematopoietic malignancies In our study, the expression of autophagy-related gene NKX2-3 was signi cantly up-regulated in prostate cancer tissues compared to the non-tumor tissues.…”

Long non-coding RNA gene regulation and trait associations across human tissues

“…NKX2-3 is a homeobox gene that is key for the development of the spleen and the visceral mesoderm, which develops several essential cell types of the gastrointestinal tract including endothelial cells, immune cells, and -notably -smooth muscle cells. Knockout mouse 30 studies have shown that loss of this gene affects spleen architecture, and lymphocyte maturation and homing (35)(36)(37)(38)(39). These findings make a compelling case that lncRNA regulation of NKX2-3 in both the colon and spleen influences ulcerative colitis susceptibility.…”