Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition

Nature Medicine

Volumn 20, Issue 9, 2014, Pages 1043-1049

  Xing, Luzhou ^a   Dai, Zhenpeng ^a   Jabbari, Ali ^a   Cerise, Jane E ^a   Higgins, Claire A ^a   Gong, Weijuan ^a   De Jong, Annemieke ^a   Harel, Sivan ^a   Destefano, Gina M ^a   Rothman, Lisa ^a   Singh, Pallavi ^a   Petukhova, Lynn ^a   MacKay Wiggan, Julian ^a   Christiano, Angela M ^a   Clynes, Raphael ^a  

^a Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

JANUS KINASE; PROTEIN KINASE INHIBITOR;

ALOPECIA AREATA; ANIMAL; ARTICLE; C3H MOUSE; CYTOTOXIC T LYMPHOCYTE; DRUG ANTAGONISM; GENE EXPRESSION PROFILING; HUMAN; IMMUNOLOGY; METABOLISM; MOUSE; SKIN;

ALOPECIA AREATA; ANIMALS; GENE EXPRESSION PROFILING; HUMANS; JANUS KINASES; MICE; MICE, INBRED C3H; PROTEIN KINASE INHIBITORS; SKIN; T-LYMPHOCYTES, CYTOTOXIC;

EID: 84908315856     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm.3645     Document Type: Article

References (29)

1. Gilhar, A., Etzioni, A., Paus, R. Alopecia areata. N. Engl. J. Med. 366, 1515-1525 (2012).
2. Petukhova, L. et al. Genome-wide association study in alopecia areata implicates both innate and adaptive immunity. Nature 466, 113-117 (2010).
3. Gilhar, A., Ullmann, Y., Berkutzki, T., Assy, B., Kalish, R.S. Autoimmune hair loss (alopecia areata) transferred by T lymphocytes to human scalp explants on SCID mice. J. Clin. Invest. 101, 62-67 (1998).
4. McElwee, K.J. et al. Transfer of CD8+ cells induces localized hair loss whereas CD4+/CD25? cells promote systemic alopecia areata and CD4+/CD25+cells blockade disease onset in the C3H/HeJ mouse model. J. Invest. Dermatol. 124, 947-957 (2005).
5. Ito, T. et al. Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack. J. Invest. Dermatol. 128, 1196-1206 (2008).
6. Sundberg, J.P., Cordy, W.R., King, L.E. Jr. Alopecia areata in aging C3H/HeJ mice. J. Invest. Dermatol. 102, 847-856 (1994).
7. McElwee, K.J., Boggess, D., King, L.E. Jr., Sundberg, J.P. Experimental induction of alopecia areata-like hair loss in C3H/HeJ mice using full-thickness skin grafts. J. Invest. Dermatol. 111, 797-803 (1998).
8. Bertolini, M. et al. Abnormal interactions between perifollicular mast cells and CD8+ T cells may contribute to the pathogenesis of alopecia areata. PLoS ONE 9, e94260 (2014).
9. Best, J.A. et al. Transcriptional insights into the CD8+ T cell response to infection and memory T cell formation. Nat. Immunol. 14, 404-412 (2013).
10. Bezman, N.A. et al. Molecular definition of the identity and activation of natural killer cells. Nat. Immunol. 13, 1000-1009 (2012).
11. Brajac, I., Gruber, F., Petrovecki, M., Malnar-Dragojevic, D. Interleukin-2 receptor ?-chain expression in patients with alopecia areata. Acta Dermatovenerol. Croat. ADC 12, 154-156 (2004).
12. Fehniger, T.A., Caligiuri, M.A. Interleukin 15: biology and relevance to human disease. Blood 97, 14-32 (2001).
13. Ye, W., Young, J.D., Liu, C.C. Interleukin-15 induces the expression of mRNAs of cytolytic mediators and augments cytotoxic activities in primary murine lymphocytes. Cell. Immunol. 174, 54-62 (1996).
14. Meresse, B. et al. Reprogramming of CTLs into natural killer-like cells in celiac disease. J. Exp. Med. 203, 1343-1355 (2006).
15. Saikali, P., Antel, J.P., Pittet, C.L., Newcombe, J., Arbour, N. Contribution of astrocyte-derived IL-15 to CD8 T cell effector functions in multiple sclerosis. J. Immunol. 185, 5693-5703 (2010).
16. Meresse, B. et al. Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity 21, 357-366 (2004).
17. Freyschmidt-Paul, P. et al. Interferon-?-deficient mice are resistant to the development of alopecia areata. Br. J. Dermatol. 155, 515-521 (2006).
18. Gilhar, A., Kam, Y., Assy, B., Kalish, R.S. Alopecia areata induced in C3H/HeJ mice by interferon-?: evidence for loss of immune privilege. J. Invest. Dermatol. 124, 288-289 (2005).
19. Freyschmidt-Paul, P. et al. Reduced expression of interleukin-2 decreases the frequency of alopecia areata onset in C3H/HeJ mice. J. Invest. Dermatol. 125, 945-951 (2005).
20. O'Shea, J.J., Kontzias, A., Yamaoka, K., Tanaka, Y., Laurence, A. Janus kinase inhibitors in autoimmune diseases. Ann. Rheum. Dis. 72 (suppl. 2), ii111-ii115 (2013).
21. Quintás-Cardama, A. et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood 115, 3109-3117 (2010).
22. Ghoreschi, K. et al. Modulation of innate and adaptive immune responses by tofacitinib (CP-690, 550). J. Immunol. 186, 4234-4243 (2011).
23. Eichler, G.S., Huang, S., Ingber, D.E. Gene Expression Dynamics Inspector (GEDI): for integrative analysis of expression profiles. Bioinformatics 19, 2321-2322 (2003).
24. Verstovsek, S. et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N. Engl. J. Med. 363, 1117-1127 (2010).
25. Harrison, C. et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N. Engl. J. Med. 366, 787-798 (2012).
26. Punwani, N. et al. Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J. Am. Acad. Dermatol. 67, 658-664 (2012).
27. Paus, R., Nickoloff, B.J., Ito, T.A. A 'hairy' privilege. Trends Immunol. 26, 32-40 (2005).
28. Waldmann, T.A. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat. Rev. Immunol. 6, 595-601 (2006).
29. Dolgin, E. Companies hope for kinase inhibitor JAKpot. Nat. Rev. Drug Discov. 10, 717-718 (2011).