title: CD4+TCRγδ+FoxP3+cells: An unidentified population of immunosuppressive cells towards disease progression leprosy patients.
abstract: This study, for the first time, reveals the role of M. leprae-specific CD4+TCRγδ+FoxP3+cells in the progression and pathogenesis of leprosy. Co-culture with CD4+CD25-cells suggested the immunosuppressive nature of CD4+TCRγδ+cells in dose-dependent manner. Isolation of CD4+TCRγδ+cells from leprosy patients and then culture in presence of M. leprae cell wall antigens (MLCwA) along with TGF β, IPP and IL-2 suggested that these cells are M. leprae specific. TGF-β-mediated SMAD3 signalling was turned out to be major factor towards the expression of FoxP3 in these cells. SMAD3 silencing during induction of these cells barely showed the induction of FoxP3. High density of SMAD3 binding at TGFβRII in CD4+TCRγδ+FoxP3+furthermore suggested the TGF-β-directed SMAD3 signalling in these cells. Taken together the above data, we can conclude that CD4+TCRγδ+FoxP3+cells possess the potential to track the severity of the disease in leprosy patients.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Tarique
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, India.
authors.forename: Raza A
authors.initials: RA
authors.lastname: Naqvi
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, India.
authors.forename: Riyasat
authors.initials: R
authors.lastname: Ali
authors.affiliation: Department of Dermatovenereology, All India Institute of Medical Sciences, AIIMS, New Delhi, India.
authors.forename: Neena
authors.initials: N
authors.lastname: Khanna
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, India.|GITAM Institute of Medical Sciences and Research, GITAM University, Rushikonda, Visakhapatnam, India.
authors.forename: Donthamshetty Nageswara
authors.initials: DN
authors.lastname: Rao
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D056006:Leprosy, Multibacillary / Q000097:blood / Q000276:immunology*; D056005:Leprosy, Paucibacillary / Q000097:blood / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma
keywords: CD4+TCRγδ+FoxP3+ cells; SMAD3; leprosy