Surfactant protein D-mediated decrease of allergen-induced inflammation is dependent upon CTLA4.

Area of Science:

• Immunology
• Pulmonary Medicine
• Allergy Research

Background:

• Pulmonary surfactant protein D (SP-D) is an innate immune molecule crucial for host defense.
• SP-D modulates adaptive immune responses, and SP-D deficiency in mice leads to heightened allergic reactions.
• Lymphocytes are required for SP-D induction, suggesting a role for SP-D in regulating adaptive immunity, particularly T cell responses.

Purpose of the Study:

• To investigate the potential of SP-D to decrease adaptive allergic responses through T cell interactions.
• To evaluate the efficacy of two forms of SP-D (dodecamer and SP-D NCRD) in modulating immune responses in vitro and in vivo.
• To elucidate the mechanism by which SP-D influences T cell activation and allergic responses.

Main Methods:

• Utilized two forms of SP-D: a full dodecamer and a fragment (SP-D NCRD) containing the neck and carbohydrate recognition domains.
• Assessed immune responses in vitro, including T cell proliferation and IL-2 production.
• Employed a murine model of pulmonary inflammation and allergic responses, with and without CTLA4 signal inhibition.

Main Results:

• Both SP-D forms demonstrated a decrease in immune responses in vitro and in a pulmonary inflammation model.
• SP-D NCRD treatment increased the transcription of CTLA4 (cytotoxic T-lymphocyte-associated protein 4) in T cells.
• The inhibitory effect of SP-D NCRD on lymphoproliferation and IL-2 production was abolished when CTLA4 signaling was blocked.
• In vivo administration of SP-D NCRD failed to reduce allergen-induced responses when CTLA4 was inhibited.

Conclusions:

• SP-D effectively decreases allergen-induced immune responses.
• The mechanism underlying SP-D's suppressive effect on allergic responses involves the upregulation of CTLA4 in T cells.
• SP-D represents a potential therapeutic target for managing allergic pulmonary diseases.