{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T09:42:27Z","timestamp":1771062147728,"version":"3.50.1"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0004592","type":"journal-article","created":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T17:39:01Z","timestamp":1459532341000},"page":"e0004592","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":66,"title":["Leprosy Reactions Show Increased Th17 Cell Activity and Reduced FOXP3+ Tregs with Concomitant Decrease in TGF-\u03b2 and Increase in IL-6"],"prefix":"10.1371","volume":"10","author":[{"given":"Chaman","family":"Saini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anisuddin","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkatesh","family":"Ramesh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Indira","family":"Nath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2016,4,1]]},"reference":[{"key":"ref1","first-page":"389","article-title":"Weekly epidemiological record","volume":"89","year":"2014"},{"key":"ref2","first-page":"255","article-title":"Classification of leprosy according to immunity. A five-group system","volume":"34","author":"DS Ridley","year":"1966","journal-title":"Int J Lepr Other Mycobact Dis"},{"key":"ref3","first-page":"60","article-title":"IAL Textbook of LEPROSY","author":"I Nath","year":"2010"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1111\/1523-1747.ep12381958","article-title":"Th1-Th2 paradigm: insights from leprosy","volume":"102","author":"RL Modlin","year":"1994","journal-title":"J Invest Dermatol"},{"key":"ref5","first-page":"97","article-title":"Cytokine profile of circulating T cells of leprosy patients reflects both indiscriminate and polarized T-helper subsets: T-helper phenotype is stable and uninfluenced by related antigens of Mycobacterium leprae","volume":"86","author":"N Misra","year":"1995","journal-title":"Immunology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1086\/498216","article-title":"Effective treatment of erythema nodosum leprosum with thalidomide is associated with immune stimulation","volume":"192","author":"PA Haslett","year":"2005","journal-title":"J Infect Dis"},{"key":"ref7","first-page":"388","article-title":"Immune complexes and complement hypercatabolism in patients with leprosy","volume":"26","author":"B Bjorvatn","year":"1976","journal-title":"Clin Exp Immunol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1128\/CVI.00762-12","article-title":"Lsr2 of Mycobacterium leprae and its synthetic peptides elicit restitution of T cell responses in erythema nodosum leprosum and reversal reactions in patients with lepromatous leprosy","volume":"20","author":"C Saini","year":"2013","journal-title":"Clin Vaccine Immunol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev.immunol.21.120601.141122","article-title":"Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses","volume":"22","author":"S Sakaguchi","year":"2004","journal-title":"Annu Rev Immunol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"26R","DOI":"10.1203\/PDR.0b013e31819e76c7","article-title":"The T(reg)\/Th17 cell balance: a new paradigm for autoimmunity","volume":"65","author":"EM Eisenstein","year":"2009","journal-title":"Pediatr Res"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.cytogfr.2010.10.004","article-title":"IL-17 and Th17 cells in tuberculosis","volume":"21","author":"E Torrado","year":"2010","journal-title":"Cytokine Growth Factor Rev"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/pr.2015.143","article-title":"The role of Th17 and Treg responses in the pathogenesis of RSV infection","volume":"78","author":"TC Mangodt","year":"2015","journal-title":"Pediatr Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"11511","DOI":"10.1038\/srep11511","article-title":"Th17 and Th17\/Treg ratio at early HIV infection associate with protective HIV-specific CD8(+) T-cell responses and disease progression","volume":"5","author":"J Falivene","year":"2015","journal-title":"Sci Rep"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/ni0407-345","article-title":"T(H)-17 cells in the circle of immunity and autoimmunity","volume":"8","author":"E Bettelli","year":"2007","journal-title":"Nat Immunol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1038\/ni1261","article-title":"A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17","volume":"6","author":"H Park","year":"2005","journal-title":"Nat Immunol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1365-2567.2008.03017.x","article-title":"Interleukin-17 in host defence against bacterial, mycobacterial and fungal pathogens","volume":"126","author":"MM Curtis","year":"2009","journal-title":"Immunology"},{"key":"ref17","article-title":"The Biological Functions of T Helper 17 Cell Effector Cytokines in Inflammation","volume":"28","author":"JKK Wenjun Ouyang","year":"2004","journal-title":"Cell Immunity"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/nature05505","article-title":"Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis","volume":"445","author":"Y Zheng","year":"2007","journal-title":"Nature"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1002\/eji.200890012","article-title":"Regulatory T cells in the past and for the future","volume":"38","author":"S Sakaguchi","year":"2008","journal-title":"Eur J Immunol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nature04753","article-title":"Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells","volume":"441","author":"E Bettelli","year":"2006","journal-title":"Nature"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nature07021","article-title":"IL-21 and TGF-beta are required for differentiation of human T(H)17 cells","volume":"454","author":"L Yang","year":"2008","journal-title":"Nature"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/nature06878","article-title":"TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function","volume":"453","author":"L Zhou","year":"2008","journal-title":"Nature"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nature05970","article-title":"IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells","volume":"448","author":"T Korn","year":"2007","journal-title":"Nature"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/ni1488","article-title":"IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways","volume":"8","author":"L Zhou","year":"2007","journal-title":"Nat Immunol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"e2639","DOI":"10.1371\/journal.pntd.0002639","article-title":"Increase in TGF-beta secreting CD4(+)CD25(+) FOXP3(+) T regulatory cells in anergic lepromatous leprosy patients","volume":"8","author":"C Saini","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"e2773","DOI":"10.1371\/journal.pntd.0002773","article-title":"T-cell regulation in lepromatous leprosy","volume":"8","author":"K Bobosha","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e2338","DOI":"10.1371\/journal.pntd.0002338","article-title":"CD4+ Th17 cells discriminate clinical types and constitute a third subset of non Th1, Non Th2 T cells in human leprosy","volume":"7","author":"C Saini","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"key":"ref28","article-title":"Increased Serum Circulatory Levels of Interleukin 17F in Type 1 Reactions of Leprosy","author":"ML Sundeep Chaitanya","year":"2012","journal-title":"J Clin Immunol"},{"key":"ref29","first-page":"77","article-title":"Reactions in leprosy","volume":"40","author":"DS Ridley","year":"1969","journal-title":"Lepr Rev"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/ni1496","article-title":"Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells","volume":"8","author":"EV Acosta-Rodriguez","year":"2007","journal-title":"Nat Immunol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1074\/jbc.M207577200","article-title":"Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17","volume":"278","author":"S Aggarwal","year":"2003","journal-title":"J Biol Chem"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s10875-013-9979-x","article-title":"Longitudinal immune responses and gene expression profiles in type 1 leprosy reactions","volume":"34","author":"A Geluk","year":"2014","journal-title":"J Clin Immunol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"7948","DOI":"10.4049\/jimmunol.180.12.7948","article-title":"Regulation of IL-17 in human CCR6+ effector memory T cells","volume":"180","author":"H Liu","year":"2008","journal-title":"J Immunol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.immuni.2008.03.001","article-title":"Th17 cell differentiation: the long and winding road","volume":"28","author":"MJ McGeachy","year":"2008","journal-title":"Immunity"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/ni.1613","article-title":"A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses","volume":"9","author":"E Volpe","year":"2008","journal-title":"Nat Immunol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/ni1497","article-title":"Development, cytokine profile and function of human interleukin 17-producing helper T cells","volume":"8","author":"NJ Wilson","year":"2007","journal-title":"Nat Immunol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.clindermatol.2014.07.005","article-title":"Immunology of leprosy and diagnostic challenges","volume":"33","author":"I Nath","year":"2015","journal-title":"Clin Dermatol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1128\/CMR.19.2.338-381.2006","article-title":"The continuing challenges of leprosy","volume":"19","author":"DM Scollard","year":"2006","journal-title":"Clin Microbiol Rev"},{"issue":"Suppl 3","key":"ref39","doi-asserted-by":"crossref","first-page":"iii26","DOI":"10.1136\/ard.2008.098004","article-title":"Th17 cells in immunity and autoimmunity","volume":"67","author":"M Oukka","year":"2008","journal-title":"Ann Rheum Dis"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/eji.200636435","article-title":"Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells","volume":"37","author":"J Wang","year":"2007","journal-title":"Eur J Immunol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1128\/CVI.05214-11","article-title":"Imbalance of Th17 cells and regulatory T cells in tuberculous pleural effusion","volume":"18","author":"ZJ Ye","year":"2011","journal-title":"Clin Vaccine Immunol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1038\/mi.2014.136","article-title":"Immune requirements for protective Th17 recall responses to Mycobacterium tuberculosis challenge","volume":"8","author":"L Monin","year":"2015","journal-title":"Mucosal Immunol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1093\/intimm\/dxn106","article-title":"The phenotype of human Th17 cells and their precursors, the cytokines that mediate their differentiation and the role of Th17 cells in inflammation","volume":"20","author":"F Annunziato","year":"2008","journal-title":"Int Immunol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1002\/eji.201040391","article-title":"IL-6: Regulator of Treg\/Th17 balance","volume":"40","author":"Akihiro Kimura","year":"2010","journal-title":"Eur J Immunol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/sj.icb.7100114","article-title":"Autoimmunity: IL-21: a new player in Th17-cell differentiation","volume":"85","author":"EK Deenick","year":"2007","journal-title":"Immunol Cell Biol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1038\/ni1539","article-title":"TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology","volume":"8","author":"MJ McGeachy","year":"2007","journal-title":"Nat Immunol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"5948","DOI":"10.4049\/jimmunol.181.9.5948","article-title":"IL-23 promotes maintenance but not commitment to the Th17 lineage","volume":"181","author":"GL Stritesky","year":"2008","journal-title":"J Immunol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1093\/abbs\/gmt049","article-title":"Recruitment of CCR6-expressing Th17 cells by CCL20 secreted from plasmin-stimulated macrophages","volume":"45","author":"Q Li","year":"2013","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/1471-2334-9-75","article-title":"Potential plasma markers of Type 1 and Type 2 leprosy reactions: a preliminary report","volume":"9","author":"MM Stefani","year":"2009","journal-title":"BMC Infect Dis"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.4049\/jimmunol.1000597","article-title":"CCL20 and beta-defensin-2 induce arrest of human Th17 cells on inflamed endothelium in vitro under flow conditions","volume":"186","author":"S Ghannam","year":"2011","journal-title":"J Immunol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3109\/03009742.2014.952332","article-title":"Increase in Th17-associated CCL20 and decrease in Th2-associated CCL22 plasma chemokines in active ANCA-associated vasculitis","volume":"44","author":"P Eriksson","year":"2015","journal-title":"Scand J Rheumatol"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0004592","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T21:55:54Z","timestamp":1540331754000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0004592"}},"subtitle":[],"editor":[{"given":"Christian","family":"Johnson","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,4,1]]},"references-count":51,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2016,4,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0004592","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,1]]}}}