c-Rel

c-Rel, a member of the NF-κB/Rel transcription factor family, functions as a central regulator of immune cell proliferation, survival, and effector activity, particularly in hematopoietic lineages^[1][2]. Mechanistically, c-Rel directly regulates transcription of genes essential for T-cell differentiation, including Il2 and Foxp3, and controls IL-12 and IL-23 production in macrophages and dendritic cells, thereby influencing adaptive immunity^[2][3]. Compared with other NF-κB isoforms, c-Rel exhibits tissue-restricted expression, predominantly in lymphoid cells, and demonstrates non-redundant phenotypes in knockout models, indicating unique regulatory functions^[1][2]. In disease contexts, aberrant c-Rel activation is implicated in B cell lymphomas, autoimmune disorders, and graft-versus-host disease, with c-Rel deficiency mitigating GVHD while preserving graft-versus-leukemic effects in murine transplantation models^[4][5]. Experimental applications leverage c-Rel modulation via genetic knockout or pharmacological inhibition, highlighting its potential as a target for immunomodulation and cancer therapy^[2][5][6]. Selective inhibitors, including protein kinase C (PKC) modulators, can suppress c-Rel-dependent transcription without affecting DNA binding, providing isoform-specific intervention opportunities^[6]. Overall, the distinct signaling, isoform-specific expression, and disease relevance of c-Rel underpin its value in mechanistic studies and therapeutic design.