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As hypopigmentation appears consistently in PKDL, especially the macular form, this study aimed to delineate immune factors that singly or in combination could contribute towards this hypopigmentation. At lesional sites, the presence of melanocytes and CD8<jats:sup>+<\/jats:sup> T\u2010cells was assessed by immunohistochemistry and mRNA expression of melanogenic markers (tyrosinase, tyrosinase\u2010related protein\u20101 and MITF) by droplet digital PCR, while plasma levels of cytokines and chemokines were measured by a multiplex assay. In comparison with skin from healthy individuals, macular PKDL demonstrated a near total absence of Melan\u2010A<jats:sup>+<\/jats:sup> cells at dermal sites, while the polymorphic cases demonstrated a 3.2\u2010fold decrease, along with a dramatic reduction in the expression of key enzymes related to the melanogenesis signalling pathway in both forms. The levels of circulating IFN\u2010\u03b3, IL\u20106, IL\u20102, IL\u20101\u03b2, TNF\u2010\u03b1 and IFN\u2010\u03b3\u2010inducible chemokines (CXCL9\/10\/11) were elevated and was accompanied by an increased lesional infiltration of CD8<jats:sup>+<\/jats:sup> T\u2010cells. The proportion of CD8<jats:sup>+<\/jats:sup> T\u2010cells correlated strongly with plasma levels of IFN\u2010\u03b3 (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.8), IL\u20106 (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.9, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), IL\u20102 (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.7), TNF\u2010\u03b1 (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.9, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and IL\u20101\u03b2 (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.7), as also with CXCL9 (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.5) and CXCL10 (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.6). Taken together, the absence\/reduction in Melan\u2010A suggested hypopigmentation in PKDL was associated with the destruction of melanocytes, following the impairment of the melanogenesis pathway. Furthermore, the presence of CD8<jats:sup>+<\/jats:sup> T\u2010cells and an enhanced IFN\u2010\u03b3\u2010associated immune milieu suggested the generation of a pro\u2010inflammatory landscape that facilitated melanocyte dysfunction\/destruction.<\/jats:p>","DOI":"10.1111\/exd.14760","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T05:46:11Z","timestamp":1676007971000},"page":"740-751","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Does immune dysregulation contribute towards development of hypopigmentation in Indian post kala\u2010azar dermal leishmaniasis?"],"prefix":"10.1111","volume":"32","author":[{"given":"Ritika","family":"Sengupta","sequence":"first","affiliation":[{"name":"Department of Pharmacology Institute of Post Graduate Medical Education and Research  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sneha","family":"Mitra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Institute of Post Graduate Medical Education and Research  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishwarya","family":"Dighal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Institute of Post Graduate Medical Education and Research  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srija","family":"Moulik","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Institute of Post Graduate Medical Education and Research  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surya Jyati","family":"Chaudhuri","sequence":"additional","affiliation":[{"name":"Sarat Chandra Chattopadhyay Government Medical College &amp; 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