lnterleukin-16: the ins and outs of regulating T-cell activation.
Intcrleukin-16 (IL-16) was originally identified in 1980 as the first-described T-cell chemoattractant. Since that time, the protein has been cloned, sequenced, and characterized in terms of expression and biologic function for regulating inflammation. Generated as a precursor molecule, IL-16 is cleaved by caspase-3, yielding pro-IL-16 and the secreted (mature) portion. Both components of IL-16 are now known to regulate T-cell growth and represent one of the few proteins for which function has been determined for both the pro- and secreted portions. Secreted IL-16 primes CD4+ T cells for IL-2 and IL-15 responsiveness, with a preferential effect on TH1 cells. Animal models have identified its involvement in the establishment of TH1-type inflammation with a critical role in the development of certain autoimmune diseases. Nuclear pro-IL-16 is a recently identified regulator of Skp2 transcription and T- cell cycle progression, acting as a scaffold protein for GABPbeta and histone deacctylase-3. The intent of this review is to present an update on the structure of both IL-16 and pro-IL-16, the biologic functions of both components, and how the functions relate to the pathology of certain diseases where changes in IL-16 expression levels have been detected.
Cruikshank
William
W
Pulmonary Center, R-304, Boston University School of Medicine, 715 Albany St., Boston, MA 02118, USA. bcruiksh@bu.com
Little
Frederic
F
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019410:Interleukin-16 / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D019410:Interleukin-16; D011498:Protein Precursors; D019707:Receptors, Chemokine; C105950:interleukin 16 precursor