Facial melanoses (FM) are a common presentation in Indian patients, causing cosmetic disfigurement with considerable psychological impact. Some of the well defined causes of FM include melasma, Riehl's melanosis, Lichen planus pigmentosus, erythema dyschromicum perstans (EDP), erythrosis, and poikiloderma of Civatte. But there is considerable overlap in features amongst the clinical entities. Etiology in most of the causes is unknown, but some factors such as UV radiation in melasma, exposure to chemicals in EDP, exposure to allergens in Riehl's melanosis are implicated. Diagnosis is generally based on clinical features. The treatment of FM includes removal of aggravating factors, vigorous photoprotection, and some form of active pigment reduction either with topical agents or physical modes of treatment. Topical agents include hydroquinone (HQ), which is the most commonly used agent, often in combination with retinoic acid, corticosteroids, azelaic acid, kojic acid, and glycolic acid. Chemical peels are important modalities of physical therapy, other forms include lasers and dermabrasion.

Regulatory B cells (Bregs) are known to exhibit their regulatory functions through interleukin-10 (IL-10) cytokine which suppress inflammation. There are only a few studies explaining the phenotype and functioning of these cells in contribution to host immunity in leprosy. Here, we evaluated the role of IL-10 producing Bregs in the pathogenesis of leprosy and assessed their immunoregulatory effects on Tregs and effector T cells. We found an increased frequency of Bregs and increased expression of their immune modulatory molecules (IL-10, FoxP3, and PDL-1) in leprosy patients. The potential immunoregulatory mechanism of Bregs was also investigated using MACS sorted Teff (CD4+CD25−) and Treg (CD4+CD25+) cells were cocultured with Bregs to elucidate the effects of Bregs on effector T and regulatory T cells. Cell coculture results showed that purified Bregs cells from leprosy patients convert CD4+CD25− cells into CD4+CD25+ cells. Cell coculture experiments also demonstrated that leprosy derived IL-10 producing Bregs enhance FoxP3 and PD-1 expression in Tregs and enhanced Tregs activity. Blocking of IL-10 receptor confirmed that IL-10 producing Breg has immunomodulatory effect on Tregs and effector T cells as effector T cells are not converted into Tregs and enhanced expression of FoxP3 and PD-1 was not observed on Tregs. Collectively, these findings demonstrate that IL-10 producing Breg cells play an important mechanism in controlling the immunopathogenesis of leprosy and have an immunomodulatory effect on Tregs and effector T cells. Our findings may pave way for novel targets of IL-10 producing Bregs for immunotherapy in leprosy patients.

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Fig 2. A patient in the oral mini-pulse group and a patient in the azathioprine group showing repigmentation with good color match after 6 months.