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Anti‐inflammatory effects in the skin of thymosin‐β4 splice‐variants
Author(s) -
Girardi Michael,
Sherling Michael A.,
Filler Renata B.,
Shires John,
Theodoridis Efstathios,
Hayday Adrian C.,
Tigelaar Robert E.
Publication year - 2003
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2003.01616.x
Subject(s) - intraepithelial lymphocyte , inflammation , thymosin , biology , immunology , lymphatic system , infiltration (hvac) , in vivo , lymph , receptor , microbiology and biotechnology , immune system , medicine , pathology , genetics , physics , thermodynamics
Summary The intraepithelial lymphocyte (IEL) network of T‐cell receptor γδ + (Vγ5 + ) dendritic epidermal T cells (DETC) in murine skin down‐regulates cutaneous inflammation, although the mechanism is unknown. Thymosin‐β4 (Tβ4), identified by serial analysis of gene expression as a predominant transcript in gut IEL, encodes both a ubiquitous actin‐binding protein (UTβ4) with demonstrated capacity to inhibit neutrophilic infiltration, and a splice‐variant limited to lymphoid tissue (LTβ4) with unknown bioactivity. Freshly isolated Vγ5 + DETCs expressed both forms, while only LTβ4 was preferentially up‐regulated after cellular activation in vitro . To compare the anti‐inflammatory properties of LTβ4 and UTβ4 in the skin in vivo , the biological activities of synthesized polypeptides were assessed using three different strategies: neutrophil infiltration by footpad λ‐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 LTβ4 were broader and most often stronger than those of UTβ4. Thus, the activation‐responsive expression of the lymph‐specific form of Tβ4 may be one mechanism by which DETC, and possibly other IELs, down‐regulate local inflammation.