Gene expression: STAT3 and RORγT in hyper IgE syndrome

Autosomal dominant hyper IgE syndrome (AD-HIES), a severe immunodeficiency disorder, is caused by a heterozygous mutation in the gene coding for the transcription factor signal transducer and activator of transcription 3 (STAT3). In healthy individuals, STAT3 resides in the cytoplasm and is phosphorylated by receptors in the cell membrane after binding of extracellular cytokines. The resulting activated protein, known as phospho-STAT3, binds a second phospho-STAT3 protein, and the resulting two-protein-complex (referred to as a “homodimer”) acts to initiate the transcription of many different genes, including the transcription factor retinoic acid-related orphan receptor gamma T (RORγT). RORγT controls important steps in the maturation process of T cells, and mutations affecting the STAT3 gene associated with AD-HIES manifest themselves in reduced populations of functional T cells.

In order to better understand the relationship between the transcription of STAT3 and RORγT in AD-HIES, researchers used a quantitative polymerase chain reaction assay to measure non-mutated STAT3 and RORγT messenger RNA (mRNA) levels in T cells derived from AD-HIES patients.

Figure 1 STAT3 and RORγT mRNA levels in T cells of AD-HIES patients and in healthy individuals (control), measured in relative units

Researchers also assessed RORγT and c-Maf expression in wild type and STAT3 deficient spleen cells, mesenteric lymph node (mLN) and small intenstine lamina propria (siLN) cells. c-Maf is a transcription factor that promotes RORγt expression and the differentiation of intestinal RORγt${}^{+}$‍ T cells. Results are shown in Figure 2.

Figure 2 Expression of RORγt (A) and c-Maf (B) in wild type (WT) and STAT3 deficient (STAT3${}^{\text{CD4 KO}}$‍) cells