Pemphigus vulgaris (PV) is an autoimmune bullous skin disease characterized by Abs to the desmosomal cadherin desmoglein-3. Although the autoantibodies have been shown to be pathogenic, the role of the cellular immune system in the pathology of pemphigus-induced acantholysis is unclear. To further delineate the potential role of T cell-signaling pathways in the pathogenesis of PV, we performed passive transfer experiments with PV IgG in gene-targeted mutant mice. Our results demonstrated that CD28-deficient mice (lacking a costimulatory signal for T cell activation) are 5-fold more sensitive to the development of PV than wild-type mice. To evaluate whether the higher incidence of disease was due to an impairment in intercellular adhesion of keratinocytes, we performed an in vitro acantholysis, using CD28(-/-) mice keratinocytes. No alteration in in vitro adhesion was detected in CD28(-/-)-type keratinocytes. Because the CD28 molecule plays a pivotal role in the induction of Th2 cytokines, we examined the levels of a prototypic Th2 cytokine (IL-10) in CD28(-/-) mice. Lower levels of IL-10 mRNA were found in lesions from CD28(-/-) mice. To determine whether pemphigus susceptibility in CD28(-/-) was related to IL-10 deficiency, we performed passive transfer experiments in IL-10(-/-) mice that demonstrated increased blisters compared with controls. To confirm that IL-10 is involved in the pathogenesis, rIL-10 was given with PV IgG. IL-10 significantly suppressed the disease activity. These data suggest a potential role of IL-10 in PV.

Immune modulation in pemphigus vulgaris: Role of CD28 and IL-10 / Toto, P. a.; Feliciani, C.; a and, Amerio; and Suzuki, P. a.; and Wang, H. b.; and Shivji, B. b.; and Woodley, G. M. b.; d and Sauder, D. c.; D. N. b., E. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 164:1(2000), pp. 522-529.

Immune modulation in pemphigus vulgaris: Role of CD28 and IL-10

Feliciani C.
Membro del Collaboration Group
;
2000-01-01

Abstract

Pemphigus vulgaris (PV) is an autoimmune bullous skin disease characterized by Abs to the desmosomal cadherin desmoglein-3. Although the autoantibodies have been shown to be pathogenic, the role of the cellular immune system in the pathology of pemphigus-induced acantholysis is unclear. To further delineate the potential role of T cell-signaling pathways in the pathogenesis of PV, we performed passive transfer experiments with PV IgG in gene-targeted mutant mice. Our results demonstrated that CD28-deficient mice (lacking a costimulatory signal for T cell activation) are 5-fold more sensitive to the development of PV than wild-type mice. To evaluate whether the higher incidence of disease was due to an impairment in intercellular adhesion of keratinocytes, we performed an in vitro acantholysis, using CD28(-/-) mice keratinocytes. No alteration in in vitro adhesion was detected in CD28(-/-)-type keratinocytes. Because the CD28 molecule plays a pivotal role in the induction of Th2 cytokines, we examined the levels of a prototypic Th2 cytokine (IL-10) in CD28(-/-) mice. Lower levels of IL-10 mRNA were found in lesions from CD28(-/-) mice. To determine whether pemphigus susceptibility in CD28(-/-) was related to IL-10 deficiency, we performed passive transfer experiments in IL-10(-/-) mice that demonstrated increased blisters compared with controls. To confirm that IL-10 is involved in the pathogenesis, rIL-10 was given with PV IgG. IL-10 significantly suppressed the disease activity. These data suggest a potential role of IL-10 in PV.
2000
Immune modulation in pemphigus vulgaris: Role of CD28 and IL-10 / Toto, P. a.; Feliciani, C.; a and, Amerio; and Suzuki, P. a.; and Wang, H. b.; and Shivji, B. b.; and Woodley, G. M. b.; d and Sauder, D. c.; D. N. b., E. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 164:1(2000), pp. 522-529.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2862923
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