BACKGROUND: Systemic lupus erythematosus (SLE) is associated with a numerical and functional reduction of peripheral blood (PB) invariant natural killer T (iNKT) cells. Limited information exists on the role of iNKT cells in the pathogenesis of lupus erythematosus. OBJECTIVE: To investigate the frequency and phenotype of iNKT cells in PB and dermal infiltrates from patients with SLE, subacute-cutaneous lupus erythematosus (SCLE) and discoid lupus erythematosus (DLE). METHODS: PB was obtained from 23 SLE, 6 SCLE, and 11 DLE patients, and from 30 healthy controls. iNKT cell frequency and CCR4/CCR6 surface expression were assessed by flow cytometry. The frequency and phenotype of skin infiltrating Vα24(+)Vβ11(+) iNKT cells were investigated by immunofluorescence in lesional biopsies from 20 patients, unaffected skin from 3 patients, and from 6 healthy controls. RESULTS: Lupus erythematosus patients displayed significantly lower percentages of circulating CD3(+)6B11(+) iNKT cells compared to healthy controls. Whereas CCR6 expression on iNKT cells was enhanced in active SLE patients regardless of cutaneous involvement compared to healthy controls, CCR4 was exclusively increased in patients with active cutaneous lesions. Furthermore, iNKT cells were significantly enriched in lesional skin of SLE and DLE patients, but not in unaffected skin of lupus patients. The majority of lesional iNKT cells expressed IFN-γ and CCR4. CONCLUSION: The deficiency in circulating iNKT cells in cutaneous lupus erythematosus is associated with an increase of iNKT cells at the site of cutaneous inflammation. These data underscore the importance of analyzing iNKT cells not only in PB, but also in the target tissues.
BACKGROUND: Systemic lupus erythematosus (SLE) is associated with a numerical and functional reduction of peripheral blood (PB) invariant natural killer T (iNKT) cells. Limited information exists on the role of iNKT cells in the pathogenesis of lupus erythematosus. OBJECTIVE: To investigate the frequency and phenotype of iNKT cells in PB and dermal infiltrates from patients with SLE, subacute-cutaneous lupus erythematosus (SCLE) and discoid lupus erythematosus (DLE). METHODS: PB was obtained from 23 SLE, 6 SCLE, and 11 DLE patients, and from 30 healthy controls. iNKT cell frequency and CCR4/CCR6 surface expression were assessed by flow cytometry. The frequency and phenotype of skin infiltrating Vα24(+)Vβ11(+) iNKT cells were investigated by immunofluorescence in lesional biopsies from 20 patients, unaffected skin from 3 patients, and from 6 healthy controls. RESULTS: Lupus erythematosus patients displayed significantly lower percentages of circulating CD3(+)6B11(+) iNKT cells compared to healthy controls. Whereas CCR6 expression on iNKT cells was enhanced in active SLE patients regardless of cutaneous involvement compared to healthy controls, CCR4 was exclusively increased in patients with active cutaneous lesions. Furthermore, iNKT cells were significantly enriched in lesional skin of SLE and DLE patients, but not in unaffected skin of lupus patients. The majority of lesional iNKT cells expressed IFN-γ and CCR4. CONCLUSION: The deficiency in circulating iNKT cells in cutaneous lupus erythematosus is associated with an increase of iNKT cells at the site of cutaneous inflammation. These data underscore the importance of analyzing iNKT cells not only in PB, but also in the target tissues.
Authors: L Tordesillas; N Cubells-Baeza; C Gómez-Casado; C Berin; V Esteban; W Barcik; L O'Mahony; C Ramirez; L F Pacios; M Garrido-Arandia; A Díaz-Perales Journal: Clin Exp Allergy Date: 2017-07-14 Impact factor: 5.018
Authors: Lei Shen; Hong Zhang; Maria Caimol; Claudia J Benike; Eliza F Chakravarty; Samuel Strober; Edgar G Engleman Journal: Eur J Immunol Date: 2014-11-27 Impact factor: 5.532
Authors: Colton J Garelli; Maggi Ahmed Refat; Padma P Nanaware; Zaida G Ramirez-Ortiz; Mehdi Rashighi; Jillian M Richmond Journal: Front Immunol Date: 2020-07-02 Impact factor: 7.561