Human Semaphorin-4A drives Th2 responses by
binding to receptor ILT-4
, Ying Li
, Zhiqiang Zhang
, Junji Xing
, Ying Sun
, Sheng Yao
& Lieping Chen
Semaphorin-4A (Sema4A) has been implicated in the co-stimulation of T cells and drives
Th1 immune responses by binding to the receptor T-cell immunoglobulin and mucin
domain protein 2 (Tim-2) in mice. Here we show that human, but not murine, Sema4A is
preferentially expressed on antigen-presenting cells, and co-stimulates CD4
proliferation and drives Th2 responses. By employing two independent cloning strategies,
we demonstrate that Immunoglobulin-like transcript 4 (ILT-4) is a receptor for human
SEMA4A (hSEMA4A) on activated CD4
T cells. We also ﬁnd hSEMA4A to be highly
expressed in human asthmatic lung tissue, implying its potential function in disease
pathogenesis. Our study deﬁnes a different biological function of hSEMA4A from its murine
homolog through its binding to the receptor of ILT-4 to co-stimulate CD4
T cells and
regulate Th2 cells differentiation.
CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Department of Immunology
and Center for Cancer Immunology Research, The University of Texas M.D. Anderson Cancer Center, Houston TX 77030, USA.
Transplant Research, Houston Methodist Hospital and Methodist Hospital Research Institute, Texas Medical Center, Houston TX 77030, USA.
Asthma, Allergy and Lung Biology, MRC-Asthma UK Centre for Allergic Mechanisms of Asthma, King’s College London, London SE1 1YZ, UK.
of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Department of Immunobiology, Medicine and
Dermatology, Cancer Immunology Program at Yale Cancer Center, Yale University School of Medicine, New Haven CT 06519, USA.
Oncology and Cellular
Therapy, TopAlliance Biosciences, Rockville MD 20850, USA. Correspondence and requests for materials should be addressed to
N.L. (email: firstname.lastname@example.org)