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Critical role of TSLP-responsive mucosal dendritic cells in the induction of nasal antigen-specific IgA response.
- Source :
-
Mucosal immunology [Mucosal Immunol] 2017 Jul; Vol. 10 (4), pp. 901-911. Date of Electronic Publication: 2016 Dec 07. - Publication Year :
- 2017
-
Abstract
- Thymic stromal lymphopoietin (TSLP) is an interleukin-7 (IL-7)-like cytokine involved in T helper 2 type immune responses. The primary target of TSLP is myeloid dendritic cells (DCs), however, little is known about the mechanism by which TSLP elicits respiratory IgA immune responses upon mucosal immunization. Here, we found that the levels of TSLP and TSLPR were upregulated in the mucosal DCs of mice nasally immunized with pneumococcal surface protein A (PspA) plus cholera toxin (CT) compared with those immunized with PspA alone. PspA-specific IgA responses, but not IgG Ab responses were significantly reduced in both serum and mucosal secretions of TSLPR knockout mice compared with wild-type mice after nasal immunization with PspA plus CT. Furthermore, CD11c <superscript>+</superscript> mucosal DCs isolated from TSLPR knockout mice nasally immunized with PspA plus CT were less activated and exhibited markedly reduced expression of IgA-enhancing cytokines (e.g., APRIL, BAFF, and IL-6) compared with those from equivalently immunized wild-type mice. Finally, exogenous TSLP promoted production of IgAs in an in vitro DC-B cell co-culture system as exhibited by enhanced IL-6 production. These results suggest that TSLP-TSLPR signaling is pivotal in the induction of nasal respiratory immunity against pathogenic pneumococcal infection.
- Subjects :
- Administration, Intranasal
Animals
Antibodies, Bacterial metabolism
CD11c Antigen metabolism
Cells, Cultured
Coculture Techniques
Immunity, Humoral
Immunization
Immunoglobulin A metabolism
Immunoglobulins genetics
Mice
Mice, Inbred BALB C
Mice, Knockout
Receptors, Cytokine genetics
Thymic Stromal Lymphopoietin
B-Lymphocytes immunology
Bacterial Proteins immunology
Cholera Toxin immunology
Cytokines metabolism
Dendritic Cells immunology
Immunoglobulins metabolism
Receptors, Cytokine metabolism
Respiratory Mucosa pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1935-3456
- Volume :
- 10
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Mucosal immunology
- Publication Type :
- Academic Journal
- Accession number :
- 27924821
- Full Text :
- https://doi.org/10.1038/mi.2016.103