Anti-inflammatory effects in the skin of thymosin-beta4 splice-variants

Immunology. 2003 May;109(1):1-7. doi: 10.1046/j.1365-2567.2003.01616.x.


The intraepithelial lymphocyte (IEL) network of T-cell receptor gammadelta+ (Vgamma5+) dendritic epidermal T cells (DETC) in murine skin down-regulates cutaneous inflammation, although the mechanism is unknown. Thymosin-beta4 (Tbeta4), identified by serial analysis of gene expression as a predominant transcript in gut IEL, encodes both a ubiquitous actin-binding protein (UTbeta4) with demonstrated capacity to inhibit neutrophilic infiltration, and a splice-variant limited to lymphoid tissue (LTbeta4) with unknown bioactivity. Freshly isolated Vgamma5+ DETCs expressed both forms, while only LTbeta4 was preferentially up-regulated after cellular activation in vitro. To compare the anti-inflammatory properties of LTbeta4 and UTbeta4 in the skin in vivo, the biological activities of synthesized polypeptides were assessed using three different strategies: neutrophil infiltration by footpad lambda-carrageenan injection; irritant contact dermatitis to 12-O-tetradecanoylphorbol 13-acetate; and allergic contact dermatitis to 2,4-dinitrofluorobenzene. These studies clearly showed that the anti-inflammatory activities of LTbeta4 were broader and most often stronger than those of UTbeta4. Thus, the activation-responsive expression of the lymph-specific form of Tbeta4 may be one mechanism by which DETC, and possibly other IELs, down-regulate local inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Biological Assay
  • Cells, Cultured
  • Dendritic Cells / metabolism*
  • Dermatitis, Allergic Contact / drug therapy
  • Dermatitis, Contact / drug therapy*
  • Dermatitis, Irritant / drug therapy
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Microfilament Proteins / therapeutic use*
  • Receptors, Antigen, T-Cell, gamma-delta / analysis
  • Skin / metabolism
  • Thymosin / genetics*


  • Anti-Inflammatory Agents
  • Microfilament Proteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • thymosin beta(4)
  • Thymosin