CD28 ligation in the absence of TCR stimulation up-regulates IL-17A and pro-inflammatory cytokines in relapsing-remitting multiple sclerosis T lymphocytes

Cristina Camperio (1) , Michela Muscolini (1) , Elisabetta Volpe (2) , Diletta Di Mitri (2) , Rosella Mechelli (3) , Mc Buscarinu (3) , Serena Ruggieri (4) , Enza Piccolella (1) , Marco Salvetti (3) , Claudio Gasperini (4) , Luca Battistini (2) , Loretta Tuosto (1)

1 Department of Biology and Biotechnology "Charles Darwin"
2 Neuroimmunology Unit
3 CENTERS - Neurology and Center for Experimental Neurological Therapies
4 Department of Neurosciences

CD28 is a crucial costimulatory receptor necessary full T cell activation. The role of CD28 in multiple sclerosis (MS) has been evaluated as the source of costimulatory signals integrating those delivered by TCR. However, CD28 is also able to act as a unique signaling receptor and to deliver TCR-independent autonomous signals, which regulate the expression and production of pro-inflammatory cytokines and chemokines. By comparing the cytokine/chemokine profiles of CD4 + T cells from relapsing-remitting multiple sclerosis (RRMS) patients and healthy donors (HD), we found that CD28 engagement without TCR strongly up-regulates IL-8 and IL-6 expression in RRMS compared to HD. More interestingly, in RRMS but not in HD, CD28 stimulation selectively induces the expression of IL-17A by cooperating with IL-6-mediated signals. By using specific inhibitory drugs, we also identify the phosphatidylinositol 3 kinase (PI3K) as the critical regulator of CD28 proinflammatory functions in MS.

Mots clés: Costimulation; Multiple sclerosis Inflammation; Th17 cells PI3K

Domaines: Sciences du Vivant [q-bio]; Immunologie

Cristina Camperio, Michela Muscolini, Elisabetta Volpe, Diletta Di Mitri, Rosella Mechelli, et al.. CD28 ligation in the absence of TCR stimulation up-regulates IL-17A and pro-inflammatory cytokines in relapsing-remitting multiple sclerosis T lymphocytes. Immunology Letters, 2014, 158 (1-2), pp.134-42. ⟨10.1016/j.imlet.2013.12.020⟩. ⟨pasteur-01197272⟩