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Participation of T cell immunoglobulin and mucin domain-3 (TIM-3) and its ligand (galectin-9) in the pathogenesis of active generalized vitiligo

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Abstract

Vitiligo is a depigmentary disease where melanocytes of the basal layer of epidermis are selectively destroyed by immune-cell-mediated cytotoxicity. The T cell immunoglobulin- and mucin-domain-containing molecules (TIMs) are involved in immune regulation, and their participation is not known in vitiligo. The present study revealed significant increase in the percentage of CD3+CD4+TIM3+ T cells (P < 0.05) in peripheral blood and was positively correlated with percentage body surface area involvement in aGV group. Further, increased expression of TIM-3 and its ligand galectin-9 (Gal-9) mRNA was found in peripheral blood and lesional/perilesional skin of active generalized vitiligo (aGV) compared with controls. Characteristic migration pattern of TIM-3-positive immune cells in lesional (near/in the epidermis) and perilesional (towards epidermis) skin section suggested that TIM-3+ immune cells may be involved in melanocyte destruction. Further, investigation is required to understand the role of TIM-3/Gal-9 signalling pathways in aGV and it can be targeted in the management of vitiligo.

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Acknowledgments

The present study was supported by the Department of Biotechnology (DBT), Indian Council of Medical Research (ICMR), New Delhi. We extend our sincere thanks to our laboratory research staff Mrs. Rama Lal, Mr. Pradeep Singh and Mr. Kripacharya for their kind co-operation and support.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. All India Institute of Medical Sciences, New Delhi, India

    Manoj Kumar Tembhre, Anita Singh Parihar, Alpana Sharma, Somesh Gupta, Parthaprasad Chattopadhyay & Vinod Kumar Sharma

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  1. Manoj Kumar Tembhre
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  2. Anita Singh Parihar
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Correspondence to Vinod Kumar Sharma.

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12026_2015_8632_MOESM1_ESM.jpg

Schematic representation of the gating strategies used to characterize the TIM-1 and TIM-3 expressing T cell subsets. TIM = T cell immunoglobulin and mucin domain, PHA = Phytohemagglutinin

12026_2015_8632_MOESM2_ESM.jpg

Comparison of transcript levels of TIM-3, Gal-9, TIM-1, IFN-γ and IL-4 in non-lesional (n = 15) and normal skin (n = 10). The Mann–Whitney U test was performed, and difference was significant at level of P < 0.05. The aGV (n = 15) having maximum body surface area involvement (mean ± SD = 10.93 ± 8.86) was screened from the total (n = 50) aGV patients studied. The mean ± SD of the total duration was 4.67 ± 1.92. SD = standard deviation, TIM = T cell immunoglobulin and mucin domain, Gal-9 = galectin-9, IL = interleukin, IFN = interferon and aGV = active generalized vitiligo

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Tembhre, M.K., Parihar, A.S., Sharma, A. et al. Participation of T cell immunoglobulin and mucin domain-3 (TIM-3) and its ligand (galectin-9) in the pathogenesis of active generalized vitiligo. Immunol Res 62, 23–34 (2015). https://doi.org/10.1007/s12026-015-8632-6

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