Abstract
Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine, hitherto mostly known to be involved in inflammatory responses and immunoregulation. The human tslp gene gives rise to two transcription and translation variants: a long form (lfTSLP) that is induced by inflammation, and a short, constitutively-expressed form (sfTSLP), that appears to be downregulated by inflammation. The TSLP forms can be produced by a number of cell types, including epithelial and dendritic cells (DCs). lfTSLP can activate mast cells, DCs, and T cells through binding to the lfTSLP receptor (TSLPR) and has a pro-inflammatory function. In contrast, sfTSLP inhibits cytokine secretion of DCs, but the receptor mediating this effect is unknown. Our recent studies have demonstrated that both forms of TSLP display potent antimicrobial activity, exceeding that of many other known antimicrobial peptides (AMPs), with sfTSLP having the strongest effect. The AMP activity is primarily mediated by the C-terminal region of the protein and is localized within a 34-mer peptide (MKK34) that spans the C-terminal α-helical region in TSLP. Fluorescent studies of peptide-treated bacteria, electron microscopy, and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of LL-37. Expression of TSLP in skin, oral mucosa, salivary glands, and intestine is part of the defense barrier that aids in the control of both commensal and pathogenic microbes.
Highlights
Thymic stromal lymphopoietin (TSLP) was first identified in the culture supernatant of a murine thymic stromal cell line and was shown to support B-cell growth and development [1]
Most studies hitherto have been focused on a long form of TSLP, while translation of a short form has been reported only recently [5]. lfTSLP is inducible and associated with inflammation, and sfTSLP is constitutively expressed and has an inhibiting effect on dendritic cells (DCs) [5,6]
Human TSLP Variants as Antimicrobial Peptides antimicrobial peptides (AMPs) can be classified in a variety of approaches [38], fitting into one of four major structural classes:A(1M) Plisnceaanr pbeepctliadsesisfitehdatinmaavyaardieotyptoαf -ahpeplircoaalcchoens f[o3r8m], afittitoinnguipnotonobnaectoefrifaolubrimndaijnorg;st(r2u)cβtu-srhaleet pepcltaidsseess;:((31))elxinteenardpedepptiedpetsidtheastwmitahyoavdeorp-rteαp-rheesleicnatlactioonnfoorfmspateicoinfiuc paomninboacatceirdiarlebsiindduinesg;;o(2r)(4β)-slhoeoepted peppteipdteisd[e3s9; –(431) ]e. xHteonwdeevderp,edpetridmecsidwinit,hanovAeMr-rPepserecsreentetdatiboynswofesapt egcliafnicdsam[4i2n]o, isacoifdternescildausseisfi;eodrb(a4s)ed onliotospaendiopneicpittiyd. es [39,40,41]
Summary
Thymic stromal lymphopoietin (TSLP) was first identified in the culture supernatant of a murine thymic stromal cell line and was shown to support B-cell growth and development [1]. Two variants of human TSLP peptides are expressed. LfTSLP is inducible and associated with inflammation, and sfTSLP is constitutively expressed and has an inhibiting effect on dendritic cells (DCs) [5,6].
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