CXCR4, une cible thérapeutique dans certains déficits immunitaires rares?

CXCR4 in Central and Peripheral Lymphoid Niches – Physiology, Pathology and Therapeutic Perspectives in Immune Deficiencies and Malignancies

“…The contribution of the CXCL12/CXCR4 signaling axis to many aspects of physiology and pathology has been increasingly appreciated (Figure 1 & 2). Deregulations of CXCR4 signaling and/or expression are associated with several disorders including lymphoid and autoimmune diseases, solid tumours and immune defects [15,[200][201][202][203]. Therefore, interference with the CXCL12/CXCR4 interaction or modulation of CXCR4 expression and/or activity is potentially interesting in the treatment of diseases with loss or gain of function of CXCR4.…”

“…Abnormal expression and/or activity of CXCR4 due to an over stimulation or inhibition of transcription or internalization may therefore impact on several aspects of haematopoiesis and adaptive immune response, hence immune deficits and lymphoid neoplasms. A paradigmatic disease in this respect is the WHIM syndrome in which CXCR4 is mutated and displays anomalous internalization and signaling properties [15]. More recently, one third of patients with Waldenström's macroglobilinemia, a disorder induced by an IgM-producing plasmacytoma, were shown to harbour the WHIM syndrome mutation [16].…”