T cell derived IL-10 is dispensable for tolerance induction in a murine model of allergic airway inflammation.
Regulatory mechanisms initiated by allergen-specific immunotherapy are mainly attributed to T cell derived IL-10. However, it has not been shown that T cell derived IL-10 is required for successful tolerance induction (TI). Here, we analyze cellular sources and the functional relevance of cell type specific IL-10 during TI in a murine model of allergic airway inflammation. While TI was effective in IL-10 competent mice, neutralizing IL-10 prior to tolerogenic treatment completely abrogated the beneficial effects. Cellular sources of IL-10 during TI were identified by using transcriptional reporter mice as T cells, B cells, and to a lesser extent DCs. Interestingly, TI was still effective in mice with T cell, B cell, B and T cell, or DC-specific IL-10 deficiency. In contrast, TI was not possible in mice lacking IL-10 in all hematopoetic cells, while it was effective in bone marrow (BM) chimera that lacked IL-10 only in nonhematopoetic cells. Taken together, allergen-specific tolerance depends on IL-10 from hematopoetic sources. The beneficial effects of allergen-specific immunotherapy cannot solely be attributed to IL-10 from T cells, B cells, or even DCs, suggesting a high degree of cellular redundancy in IL-10-mediated tolerance.
Allergy Research Group, Department of Dermatology, Medical Center-University of Freiburg, Freiburg, Germany.
Stefanie
S
Kunz
Allergy Research Group, Department of Dermatology, Medical Center-University of Freiburg, Freiburg, Germany.|Faculty of Biology, University of Freiburg, Freiburg, Germany.
Anja
A
Dolch
Institute of Immunology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Sangeetha
S
Surianarayanan
Allergy Research Group, Department of Dermatology, Medical Center-University of Freiburg, Freiburg, Germany.
Britta
B
Dorn
Center of Allergy and Environment (ZAUM), Member of the German Center for Lung Research (DZL), Technische Universität München and Helmholtz Zentrum München, Munich, Germany.
Mayte
M
Bewersdorff
Center of Allergy and Environment (ZAUM), Member of the German Center for Lung Research (DZL), Technische Universität München and Helmholtz Zentrum München, Munich, Germany.
Francesca
F
Alessandrini
Institute of Immunology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Rayk
R
Behrendt
Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA.
Christopher L
CL
Karp
Faculty of Life Sciences, University of Manchester, Manchester, UK.
Werner
W
Muller
Allergy Research Group, Department of Dermatology, Medical Center-University of Freiburg, Freiburg, Germany.
Stefan F
SF
Martin
Institute of Immunology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Axel
A
Roers
Allergy Research Group, Department of Dermatology, Medical Center-University of Freiburg, Freiburg, Germany.|Department of Dermatology and Allergology, University Medical Center Gießen-Marburg, Justus Liebig University Gießen, Gießen, Germany.
Thilo
T
Jakob
D000485:Allergens / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D003888:Desensitization, Immunologic; D006967:Hypersensitivity / Q000276:immunology*; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000485:Allergens; C556062:IL10 protein, mouse; D016753:Interleukin-10
Allergy; IL-10; Immunotherapy; T cells; Tolerance