02396nas a2200337   4500000000100000008004100001260001200042653001000054653000900064653001800073653001200091653001000103653001200113100001400125700001000139700001300149700001200162700001200174700001500186700001400201700001500215700001100230700001300241700001300254245011200267856008300379300000900462490000700471520156600478022001402044       2023                            d  c04/202310aIL-1010aPD-110aT cell anergy10aT cells10aTregs10aleprosy1 aTarique M1 aNaz H1 aSuhail M1 aTuran A1 aSaini C1 aMuhammad N1 aShankar H1 aZughaibi T1 aKhan T1 aKhanna N1 aSharma A00aDifferential expression of programmed death 1 (PD-1) on various immune cells and its role in human leprosy.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10161389/pdf/fimmu-14-1138145.pdf  a1-100 v143 a<p>Leprosy is a chronic bacterial disease caused by&nbsp;<em>Mycobacterium leprae</em>. Leprosy patients have been found to have defects in T cells activation, which is critical to the clearance of the bacilli. Treg cell suppression is mediated by inhibitory cytokines such as IL10, IL-35 and TGF-β and its frequency is higher in leprosy patients. Activation and overexpression of programmed death 1 (PD-1) receptor is considered to one of the pathways to inhibit T-cell response in human leprosy. In the current study we address the effect of PD-1 on Tregs function and its immuno-suppressive function in leprosy patients. Flow cytometry was used to evaluate the expression of PD-1 and its ligands on various immune cells T cells, B cells, Tregs and monocytes. We observed higher expression of PD-1 on Tregs is associated with lower production of IL-10 in leprosy patients. PD-1 ligands on T cells, B cells, Tregs and monocytes found to be higher in the leprosy patients as compared to healthy controls. Furthermore, blocking of PD-1 restores the Tregs mediated suppression of Teff and increase secretion of immunosuppressive cytokine IL-10. Moreover, overexpression of PD-1 positively correlates with disease severity as well as Bacteriological Index (BI) among leprosy patients. Collectively, our data suggested that PD-1 overexpression on various immune cells is associated with disease severity in human leprosy. Manipulation and inhibition of PD-1 signaling pathway on Tregs alter and restore the Treg cell suppression activity in leprosy patients.</p>
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