Interleukin-7: physiological roles and mechanisms of action.
Interleukin-7 (IL-7), a product of stromal cells, provides critical signals to lymphoid cells at early stages in their development. Two types of cellular responses to IL-7 have been identified in lymphoid progenitors: (1) a trophic effect and (2) an effect supporting V(D)J recombination. The IL-7 receptor is comprised of two chains, IL-7R alpha and gamma(c). Following receptor crosslinking, rapid activation of several classes of kinases occurs, including members of the Janus and Src families and PI3-kinase. A number of transcription factors are subsequently activated including STATs, c-myc, NFAT and AP-1. However, it remains to be determined which, if any, previously identified pathway leads to the trophic or V(D)J endpoints. The trophic response to IL-7 involves protecting lymphoid progenitors from a death process that resembles apoptosis. This protection is partly mediated by IL-7 induction of Bcl-2, however other IL-7-induced events are probably also involved in the trophic response. The V(D)J response to IL-7 is partly mediated through increased production of Rag proteins (which cleave the target locus) and partly by increasing the accessibility of a target locus to cleavage through chromatin remodeling.
Hofmeister
R
R
Laboratory of Molecular Immunoregulation, NCI, USA.
Khaled
A R
AR
Benbernou
N
N
Rajnavolgyi
E
E
Muegge
K
K
Durum
S K
SK
D000818:Animals; D018390:Gene Targeting; D006801:Humans; D015851:Interleukin-7 / Q000096:biosynthesis / Q000502:physiology*; D008214:Lymphocytes / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis; D011995:Recombination, Genetic; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship
D015851:Interleukin-7; D020395:Receptors, Interleukin-7