title: Primary B-cell deficiencies reveal a link between human IL-17-producing CD4 T-cell homeostasis and B-cell differentiation.
abstract: IL-17 is a pro-inflammatory cytokine implicated in autoimmune and inflammatory conditions. The development/survival of IL-17-producing CD4 T cells (Th17) share critical cues with B-cell differentiation and the circulating follicular T helper subset was recently shown to be enriched in Th17 cells able to help B-cell differentiation. We investigated a putative link between Th17-cell homeostasis and B cells by studying the Th17-cell compartment in primary B-cell immunodeficiencies. Common Variable Immunodeficiency Disorders (CVID), defined by defects in B-cell differentiation into plasma and memory B cells, are frequently associated with autoimmune and inflammatory manifestations but we found no relationship between these and Th17-cell frequency. In fact, CVID patients showed a decrease in Th17-cell frequency in parallel with the expansion of activated non-differentiated B cells (CD21(low)CD38(low)). Moreover, Congenital Agammaglobulinemia patients, lacking B cells due to impaired early B-cell development, had a severe reduction of circulating Th17 cells. Finally, we found a direct correlation in healthy individuals between circulating Th17-cell frequency and both switched-memory B cells and serum BAFF levels, a crucial cytokine for B-cell survival. Overall, our data support a relationship between Th17-cell homeostasis and B-cell maturation, with implications for the understanding of the pathogenesis of inflammatory/autoimmune diseases and the physiology of B-cell depleting therapies.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Rita R
authors.initials: RR
authors.lastname: Barbosa
authors.forename: Sara P
authors.initials: SP
authors.lastname: Silva
authors.forename: Susana L
authors.initials: SL
authors.lastname: Silva
authors.forename: Alcinda Campos
authors.initials: AC
authors.lastname: Melo
authors.forename: Elisa
authors.initials: E
authors.lastname: Pedro
authors.forename: Manuel P
authors.initials: MP
authors.lastname: Barbosa
authors.forename: M Conceição
authors.initials: MC
authors.lastname: Pereira-Santos
authors.forename: Rui M M
authors.initials: RM
authors.lastname: Victorino
authors.forename: Ana E
authors.initials: AE
authors.lastname: Sousa
mesh_terms: D000328:Adult; D000361:Agammaglobulinemia / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D017074:Common Variable Immunodeficiency / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D020381:Interleukin-17