{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T22:18:59Z","timestamp":1774736339193,"version":"3.50.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The outcome of Leishmania infections varies substantially, depending on the host and the parasite strain; infection may be asymptomatic or cause mild or severe skin ulcers (cutaneous leishmaniasis [CL]), limited or disseminated lesions, or lethal visceral disease. We previously reported an association between IL-2R mutations and susceptibility to visceral leishmaniasis in children infected with Leishmania donovani. In the present study, we evaluated the possible role of IL-2 signaling in human CL. We first showed that the transcripts of several genes of the IL-2 pathway were abundant in skin lesions caused by Leishmania braziliensis. We then carried out a genetic analysis, focusing on major genes of the IL-2 pathway. We used a family-based approach and found that polymorphisms of several genes appeared to be associated with CL in a Brazilian population. Moreover, two polymorphisms of the IL2RA gene were significantly and independently associated with CL. We confirmed this result in a second Brazilian sample (also exposed to L. braziliensis) and in Iranians infected with Leishmania tropica: IL2RA rs10905669 T (Pcombined = 6 \u00d7 10\u22127) and IL2RA rs706778 T (Pcombined = 2 \u00d7 10\u22129) were associated with greater susceptibility to lesion development. These alleles were also correlated with a poor IFN-\u03b3 response and poor FOXP3+ regulatory T cell activation. Thus, IL-2 plays a crucial role in protection against the cutaneous ulcers caused by Leishmania, and the IL-2 pathway is a potential target for strategies aiming to control Leishmania-related diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1402047","type":"journal-article","created":{"date-parts":[[2015,2,12]],"date-time":"2015-02-12T06:11:17Z","timestamp":1423721477000},"page":"2664-2672","source":"Crossref","is-referenced-by-count":22,"title":["<i>IL2RA<\/i> Genetic Variants Reduce IL-2\u2013Dependent Responses and Aggravate Human Cutaneous Leishmaniasis"],"prefix":"10.1093","volume":"194","author":[{"given":"Pablo R S","family":"Oliveira","sequence":"first","affiliation":[{"name":"Aix Marseille Universit\u00e9, G\u00e9n\u00e9tique et Immunologie des Maladies Parasitaires, Unit\u00e9 Mixte de Recherche S906 , 13385 Marseille ,","place":["France"]},{"name":"INSERM, Unit\u00e9 906 , 13385 Marseille ,","place":["France"]},{"name":"Laboratory of Pathology and Bio-Intervention, Gon\u00e7alo Moniz Research Center, Oswaldo Cruz Foundation , Salvador, Bahia 40296 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9lia","family":"Dessein","sequence":"additional","affiliation":[{"name":"Aix Marseille Universit\u00e9, G\u00e9n\u00e9tique et Immunologie des Maladies Parasitaires, Unit\u00e9 Mixte de Recherche S906 , 13385 Marseille ,","place":["France"]},{"name":"INSERM, Unit\u00e9 906 , 13385 Marseille ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Romano","sequence":"additional","affiliation":[{"name":"Aix Marseille Universit\u00e9, G\u00e9n\u00e9tique et Immunologie des Maladies Parasitaires, Unit\u00e9 Mixte de Recherche S906 , 13385 Marseille ,","place":["France"]},{"name":"INSERM, Unit\u00e9 906 , 13385 Marseille ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Cabantous","sequence":"additional","affiliation":[{"name":"Aix Marseille Universit\u00e9, G\u00e9n\u00e9tique et Immunologie des Maladies Parasitaires, Unit\u00e9 Mixte de Recherche S906 , 13385 Marseille ,","place":["France"]},{"name":"INSERM, Unit\u00e9 906 , 13385 Marseille ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria E F","family":"de Brito","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics, Department of Immunology, Aggeu Magalh\u00e3es Research Center, Oswaldo Cruz Foundation , Recife, Pernambuco 50670 420 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferrucio","family":"Santoro","sequence":"additional","affiliation":[{"name":"Aix Marseille Universit\u00e9, G\u00e9n\u00e9tique et Immunologie des Maladies Parasitaires, Unit\u00e9 Mixte de Recherche S906 , 13385 Marseille ,","place":["France"]},{"name":"INSERM, Unit\u00e9 906 , 13385 Marseille ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maira G R","family":"Pitta","sequence":"additional","affiliation":[{"name":"Aix Marseille Universit\u00e9, G\u00e9n\u00e9tique et Immunologie des Maladies Parasitaires, Unit\u00e9 Mixte de Recherche S906 , 13385 Marseille ,","place":["France"]},{"name":"INSERM, Unit\u00e9 906 , 13385 Marseille ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9ria","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics, Department of Immunology, Aggeu Magalh\u00e3es Research Center, Oswaldo Cruz Foundation , Recife, Pernambuco 50670 420 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lain C","family":"Pontes-de-Carvalho","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology and Bio-Intervention, Gon\u00e7alo Moniz Research Center, Oswaldo Cruz Foundation , Salvador, Bahia 40296 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Virmondes","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Department of Biological Sciences, Federal University of the Tri\u00e2ngulo Mineiro , Uberaba, Mina Gerais 38015 050 ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sima","family":"Rafati","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Pasteur Institute of Tehran , Tehran 1316943551 ,","place":["Iran"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Argiro","sequence":"additional","affiliation":[{"name":"Aix Marseille Universit\u00e9, G\u00e9n\u00e9tique et Immunologie des Maladies Parasitaires, Unit\u00e9 Mixte de Recherche S906 , 13385 Marseille ,","place":["France"]},{"name":"INSERM, Unit\u00e9 906 , 13385 Marseille ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain J","family":"Dessein","sequence":"additional","affiliation":[{"name":"Aix Marseille Universit\u00e9, G\u00e9n\u00e9tique et Immunologie des Maladies Parasitaires, Unit\u00e9 Mixte de Recherche S906 , 13385 Marseille ,","place":["France"]},{"name":"INSERM, Unit\u00e9 906 , 13385 Marseille ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,3,15]]},"reference":[{"key":"2025030705245360500_r1","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/S0140-6736(05)67629-5","article-title":"Advances in leishmaniasis","volume":"366","author":"Murray","year":"2005","journal-title":"Lancet"},{"key":"2025030705245360500_r2","doi-asserted-by":"crossref","first-page":"e35671","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis worldwide and global estimates of its 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