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|Title:||Surfactant protein D induces immune quiescence and apoptosis of mitogen-activated peripheral blood mononuclear cells|
Koippallil Gopalakrishnan, AR
|Citation:||Immunobiology, 2016, 221 (2), pp. 310 - 322|
|Abstract:||Surfactant Protein D (SP-D) is an integral molecule of the innate immunity secreted by the epithelial cells lining the mucosal surfaces. Its C-type lectin domain offers pattern recognition functions while it binds to putative receptors on immune cells to modify cellular functions. Activated PBMCs and increased serum levels of SP-D are observed under a range of pathophysiological conditions including infections. Thus, we speculated if SP-D can modulate systemic immune response via direct interaction with activated PBMCs. Here, we have examined interaction of a recombinant fragment of human SP-D (rhSP-D) on PHA-activated PBMCs. We observed a significant downregulation of TLR2, TLR4, CD11c and CD69 upon rhSP-D treatment. rhSP-D inhibited production of Th1 (TNF-α and IFN-γ) and Th17 (IL-17) cytokines along with IL-6. Interestingly, levels of IL-2, Th2 (IL-4) and regulatory (IL-10 and TGF-β) cytokines were unaltered. Differential expression of co-stimulatory CD28 and co-inhibitory CTLA4 expression along with their ligands CD80 and CD86 revealed selective up-regulation of CTLA4 at both mRNA and protein level. In addition, rhSP-D induced apoptosis only in the activated but not in non-activated PBMCs. Blockade of CTLA4 inhibited rhSP-D mediated apoptosis, confirming an involvement of CTLA4 in induction of apoptosis. We conclude that SP-D restores immune homeostasis: it regulates expression of immunomodulatory receptors and cytokines, which is followed by apoptosis induction of immune-activated cells. These findings appear to suggest a general role for SPD in immune surveillance against activated immune cells.|
|Appears in Collections:||Dept of Life Sciences Research Papers|
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