Russian Journal of AllergyRussian Journal of AllergyРоссийский Аллергологический Журнал1810-88302686-682XPublishing House ABV Press111510.36691/RJA1115ArticlesСтатьиTSLP (LIMFOPOETIN IZ STROMY TIMUSA) -NOVYY PATOGENETIChESKIY FAKTOR ALLERGIITSLP (ЛИМФОПОЭТИН ИЗ СТРОМЫ ТИМУСА) -НОВЫЙ ПАТОГЕНЕТИЧЕСКИЙ ФАКТОР АЛЛЕРГИИYarilinA AЯрилинА А

ГНЦ «Институт иммунологии ФМБА России», г. Москва

ГНЦ «Институт иммунологии ФМБА России», г. Москва1510200855NO5 (2008)№5 (2008)91311032020Copyright ©; 1970, Pharmarus Print MediaCopyright ©; 1970, Фармарус Принт Медиа1970Pharmarus Print MediaФармарус Принт Медиаhttps://rusalljournal.ru/raj/article/view/1115

Эпителиальные клетки тимуса и барьерных тканей секретируют цитокин, родственный интерлейки8 ну87 (IL87) - TSLP (Thymic stromal limphopoietin). Действуя на свою главную мишень - дендритные клетки, он индуцирует экспрессию мембранной молекулы OX40L. В процессе презентации антигена/ аллергена Т8лимфоциту через эту молекулу передается костимулирующий сигнал в CD4+ Т8клетку. Этот сигнал при условии отсутствия IL812 вызывает дифференцировку воспалительных Th28клеток, которые отличаются от обычных (регулирующих) Th28клеток тем, что наряду с типичными Th28ци8 токинами они вырабатывают фактор некроза опухоли, но не IL810. Результатом является индукция аллергического воспаления. Показана роль TSLP в развитии атопического дерматита и бронхиальной астмы. Формирование аллергических процессов можно предотвратить или ослабить, используя моно8 клональные антитела к OX40L, что предполагается использовать в качестве нового подхода к терапии аллергических заболеваний.

TSLP (Thymic stromal lymphopoietin)цитокинааллергияSoumelis V., Reche P.A., Kanzler H. et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat. Immunol. 2002, v. 3, p. 673680.Liu Y.J., Soumelis V., Watanabe N. et al. TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation. Annu. Rev. Immunol. 2007, v. 25, p.193219.Huston D.P., Liu Y.J. Thymic stromal lymphopoietin: a potential therapeutic target for allergy and asthma. Curr. Allergy Asthma Rep. 2006, v. 6, p. 372376.Friend S.L., Hosier S., Nelson A. et al. A thymic stromal cell line supports in vitro development of surface IgM+ B cells and produces a novel growth factor affecting B and T lineage cells. Exp. Hematol. 1994, v. 22, p. 321328.Sims J.E., Williams D.E., Morrissey P.J. et al. Molecular clon ing and biological characterization of a novel murine lymphoid growth factor. J. Exp. Med. 2000, v. 192, p. 671680.Park L.S., Martin U., Garka K., et al. Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: Formation of a functional heteromeric complex requires interleukin 7 receptor. J Exp Med. 2000, v. 192, p. 659670.Quentmeier H., Drexler H.G., Fleckenstein D., et al. Clon ing of human thymic stromal lymphopoietin (TSLP) and sig naling mechanisms leading to proliferation. Leukemia. 2001, v. 15, p. 12861292.Watanabe N., Wang Y.H., Lee H.K. et al. Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T. cells in human thymus. Nature. 2005, v. 436, p. 11811185.Ying S., O'Connor B., Ratoff J. et al. Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2attracting chemokines and disease severity. J. Immunol. 2005, v. 174, p. 81838190.Allakhverdi Z., Comeau M.R., Jessup H.K. et al. Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells. J. Exp. Med. 2007, v. 204, p. 253258.Kato A., Favoreto S. Jr, Avila P.C., Schleimer R.P. TLR3 and Th2 cytokinedependent production of thymic stromal lymphopoietin in human airway epithelial cells. J. Immu nol. 2007, v. 179, p. 10801087.Ray R.J., Furlonger C., Williams D.E., Paige C.J. Charac terization of thymic stromalderived lymphopoietin (TSLP) in murine B cell development in vitro. Eur. J. Immunol. 1996, v. 26, p. 1016Jiang Q., Coffield V.M., Kondo M., Su L. TSLP is involved in expansion of early thymocyte progenitors. BMC Immunol. 2007, v. 8, p. 11.Chappaz S., Flueck L., Farr A.G., Rolink A.G., Finke D. Increased TSLP availability restores T and Bcell compart ments in adult IL7 deficient mice. Blood. 2007, v. 110, p. 38623870. 15. AlShami A., Spolski R., Kelly J., Fry T. et al. A role for thymic stromal lymphopoietin in CD4 (+) T cell development. J. Exp. Med. 2004, v. 200, p. 159168.Carpino N., Thierfelder W.E., Chang M.S. et al. Absence of an essential role for thymic stromal lymphopoietin receptor in mu rine Bcell development. Mol. Cell. Biol. 2004, v. 24, p. 25842592.Reche P.A., Soumelis V., Gorman D.M. et al. Human thy mic stromal lymphopoietin preferentially stimulates myeloid cells. J. Immunol. 2001, v. 167, p. 336343.Osborn M.J., Ryan P.L., Kirchhof N. et al. Overexpression of murine TSLP impairs lymphopoiesis and myelopoiesis. Blood. 2004, v. 103, p. 843851.Ebner S., Nguyen V.A., Forstner M. et al. Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigenpresenting cells that induce proallergic T cells.J. Allergy Clin. Immunol. 2007, v. 119, p. 982990.Watanabe N., Hanabuchi S., Soumelis V. et al. Human thy mic stromal lymphopoietin promotes dendritic cellmediat ed CD4+ T cell homeostatic expansion. Nat. Immunol. 2004, v. 5, p. 426434.Sakaguchi S. Naturally arising CD4+ regulatory T cells for immunologic selftolerance and negative control of immune responses. Annu. Rev. Immunol. 2004, v. 22, p. 531562.Lee J.Y., Lim Y.M., Park M.J. et al. Murine thymic stromal lymphopoietin promotes the differentiation of regulatory T cells from thymic CD4(+)CD8()CD25() naive cells in a dendritic cellindependent manner. Immunol. Cell. Biol. 2008, v. 86, p. 206213.Ito T., Wang Y.H., Duramad O. et al. TSLPactivated den dritic cells induce an inflammatory T helper type 2 cell re sponse through OX40 ligand. J. Exp. Med. 2005, v. 202, p.12131223.Liu Y.J. Thymic stromal lymphopoietin and OX40 ligand pathway in the initiation of dendritic cellmediated allergic inflammation. J. Allergy Clin. Immunol. 2007, v. 120, p. 238244.So T., Song J. Sugie K. et al. Signals from OX40 regulate nuclear factor of activated T cells c1 and T cell helper 2 lineage commitment. Proc. Natl. Acad. Sci. U S A. 2006, v. 103, p. 37403745.Yoo J., Omori M., Gyarmati D. et al. Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin. J. Exp. Med. 2005, v. 202, p. 541549.Li M., Hener P., Zhang Z. et al. Topical vitamin D3 and low calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis. Proc. Natl. Acad. Sci. U S A. 2006, v. 103, p. 1173611741.AlShami A. Spolski R., Kelly J. et al. A role for TSLP in the development of inflammation in an asthma model. J.Exp. Med. 2005, v. 202, p. 829839.Zhou B., Comeau M.R., De Smedt T. et al. Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice. Nat. Immunol. 2005, v. 6, p. 10471053.Seshasayee D., Lee W.P., Zhou M. et al. In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation. J. Clin. Invest. 2007, v. 117, p. 38683878.