The Critical Role of Bach2 in Shaping the Balance between CD4⁺ T Cell Subsets in Immune-Mediated Diseases

Abstract

The transcription factor Bach2 which is predominantly expressed in B and T lymphocytes represses the expression of genes by forming heterodimers with small Maf and Batf proteins and binding to the corresponding sequence on the DNA. In this way, Bach2 serves as a highly conserved repressor which controls the terminal differentiation and maturation of both B and T lymphocytes. It is required for class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes in activated B cells, and its function in B cell differentiation has been well-described. Furthermore, emerging data show that Bach2 regulates transcriptional activity in T cells at super enhancers or regions of high transcriptional activity, thus stabilizing immunoregulatory capacity and maintaining T cell homeostasis. Bach2 is also critical for the formation and function of CD4+ T cell lineages (Th1, Th2, Th9, Th17, T follicular helper (Tfh), and regulatory T (Treg) cells). Genetic variations within Bach2 locus are associated with numerous immune-mediated diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), chronic pancreatitis (CP), type 2 chronic airway inflammation, inflammatory bowel disease (IBD), and type 1 diabetes. Here, we reveal a critical role of Bach2 in regulating T cell biology and the correlation with these immune-mediated diseases.

Characterization of rare spindle and root cell transcriptional profiles in the stria vascularis of the adult mouse cochlea

“…These data suggest that Bach2 prevents humoral autoimmunity, at least in part by inhibiting the generation of pathogenic Tfh cells. Bach2 also appears to regulate differentiation and effector functions of other T cell subsets including Treg and Th17 cells, which play prominent roles in autoimmunity when deregulated 61 , 62 . Finally, Bach2 appears to be necessary for an appropriate macrophage responses to T cell-induced inflammation 63 .…”

The Function and Role of the Th17/Treg Cell Balance in Inflammatory Bowel Disease

“…In contrast, the differentiation of Th17 cells was not now affected [ 29 ]. Bach2, a transcription factor of downstream of TCR signaling, balances TCR signal-induced transcriptional activity of IRF4 to maintain homeostasis of tTreg and pTreg cells and shapes the balance of Th17/Treg cells [ 30 , 31 ].…”

Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in systemic lupus erythematosus

“…Th9 cells, as inflammatory factor in multiple sclerosis, suppress the more intense inflammatory response of other subtypes of T cells, thus determining the severity of the disease in multiple sclerosis patients [21]. Bach2 has reported to be associated with the terminal differentiation and maturation of both B and T lymphocytes [22]. Bach2 takes part in the development of SLE by regulating the immune functions of B and T lymphocytes [23,24].…”

“…Bach2 has reported to be associated with the terminal differentiation and maturation of both B and T lymphocytes [22]. Bach2 takes part in the development of SLE by regulating the immune functions of B and T lymphocytes [23,24].…”