p38γ and p38δ Are Involved in T Lymphocyte Development

p38MAP kinase (MAPK) signal transduction pathways are essential regulators of the immune response. Particularly, p38γ and p38δ regulate many immune cell functions such as cytokine production, migration or T cell activation; however, their involvement in immune cell development is largely unknown. Here we analysed the role of p38 MAPK isoforms p38γ and p38δ in T cell differentiation in the thymus and in lymph nodes, using mice deficient in p38γ, p38δ, or in both. We found that the T cell differentiation program in the thymus was affected at different stages in p38γ-, p38δ- and p38γ/δ-deficient mice, and also peripheral T cell homeostasis was compromised. Particularly, p38δ deletion affects different stages of early CD4-CD8- double negative thymocyte development whereas lack of p38γ favours thymocyte positive selection from CD4+CD8+ double positive to CD4+ or CD8+ single positive cells. Our results identify unreported functions for p38γ and p38δ in T cells.