Neuroimmune semaphorin 4D is necessary for optimal lung allergic inflammation

K. Shanks, E. H. Nkyimbeng-Takwi, E. Smith, M. M. Lipsky, L. J. DeTolla, D. W. Scott, A. D. Keegan, S. P. Chapoval*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Neuroimmune semaphorin 4D (Sema4D) was found to be expressed and function in the nervous and immune systems. In the immune system, Sema4D is constitutively expressed on T cells and regulates T cell priming. In addition, it displays a stimulatory function on macrophages, DC, NK cells, and neutrophils. As all these cells are deeply involved in asthma pathology, we hypothesized that Sema4D plays a critical non-redundant regulatory role in allergic airway response. To test our hypothesis, we exposed Sema4D-/- and WT mice to OVA injections and challenges in the well-defined mouse model of OVA-induced experimental asthma. We observed a significant decrease in eosinophilic airway infiltration in allergen-treated Sema4D-/- mice relative to WT mice. This reduced allergic inflammatory response was associated with decreased BAL IL-5, IL-13, TGFβ1, IL-6, and IL-17A levels. In addition, T cell proliferation in OVA323-339-restimulated Sema4D-/- cell cultures was downregulated. We also found increased Treg numbers in spleens of Sema4D-/- mice. However, airway hyperreactivity (AHR) to methacholine challenges was not affected by Sema4D deficiency in either acute or chronic experimental disease setting. Surprisingly, lung DC number and activation were not affected by Sema4D deficiency. These data provide a new insight into Sema4D biology and define Sema4D as an important regulator of Th2-driven lung pathophysiology and as a potential target for a combinatory disease immunotherapy.

Original languageEnglish
Pages (from-to)480-487
Number of pages8
JournalMolecular Immunology
Issue number4
StatePublished - 31 Dec 2013
Externally publishedYes


  • Allergen
  • Asthma
  • CD72
  • Experimental models
  • Knockout mice
  • Plexin B1
  • Sema4D/CD100
  • Th2 cytokines


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