Schematic representation of trans-acting domains and molecular mechanisms of leukocyte-associated KLFs. (A) Comparison of KLF subdomains for: KLF1,⁸⁹  KLF2,^20,90  KLF3,^91,92  KLF4,⁹³  KLF5,^94,95  KLF6,⁹⁶  KLF9,^97–99  KLF10,^44,100  and KLF13.^49,50  The “zinc fingers” are represented by red boxes. The trans-activation domains are indicated by orange boxes, whereas the trans-repression domains are indicated by blue boxes. (B) Role of KLFs in regulating signaling pathways and transcriptional targets that affect leukocytes in health and disease. On activation by stimuli, such as the TCR, BCR, cytokines/growth factors, drugs (statins, rapamycin), or environmental pollutants (dioxin), the upstream cytoplasmic (eg, AKT/PI3K) or nuclear (eg, PU.1 or FOXO1) effector proteins transduce signals that can activate or inhibit nuclear KLFs. KLFs, in turn, induce or repress target genes (alone or in association with coactivators or corepressors) that affect leukocyte cell growth and differentiation, survival, activation, or homing and recruitment, ultimately affecting various disease states.