Surfactant protein D-mediated decrease of allergen-induced inflammation is dependent upon CTLA4.
Pulmonary surfactant protein D (SP-D), a member of the collectin family, is an innate immune molecule critical for defense that can also modulate adaptive immune responses. We previously showed that SP-D-deficient mice exhibit enhanced allergic responses and that SP-D induction requires lymphocytes. Thus, we postulated that SP-D may decrease adaptive allergic responses through interaction with T cells. In this study, we used two forms of SP-D, a dodecamer and a shorter fragment containing the trimeric neck and carbohydrate recognition domains (SP-D NCRD). Both forms decreased immune responses in vitro and in a murine model of pulmonary inflammation. SP-D NCRD increased transcription of CTLA4, a negative regulator of T cell activation, in T cells. SP-D NCRD no longer decreased lymphoproliferation and IL-2 cytokine production when CTLA4 signals were abrogated. Administration of SP-D NCRD in vivo no longer decreased allergen induced responses when CTLA4 was inhibited. Our results indicate that SP-D decreases allergen responses, an effect that may be mediated by increase of CTLA4 in T cells.
Lin
Ko-Wei
KW
Division of Pulmonary and Critical Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Jen
Kai Yu
KY
Suarez
Carlos Jose
CJ
Crouch
Erika C
EC
Perkins
David L
DL
Finn
Patricia W
PW
D000485:Allergens / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D060908:CTLA-4 Antigen; D004797:Enzyme-Linked Immunosorbent Assay; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000485:Allergens; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D037663:Pulmonary Surfactant-Associated Protein D; D007073:Immunoglobulin E; D010047:Ovalbumin