Mice Deficient in CD38 Develop an Attenuated Form of Collagen Type II-Induced Arthritis

Abstract

CD38, a type II transmembrane glycoprotein expressed in many cells of the immune system, is involved in cell signaling, migration and differentiation. Studies in CD38 deficient mice (CD38 KO mice) indicate that this molecule controls inflammatory immune responses, although its involvement in these responses depends on the disease model analyzed. Here, we explored the role of CD38 in the control of autoimmune responses using chicken collagen type II (col II) immunized C57BL/6-CD38 KO mice as a model of collagen-induced arthritis (CIA). We demonstrate that CD38 KO mice develop an attenuated CIA that is accompanied by a limited joint induction of IL-1β and IL-6 expression, by the lack of induction of IFNγ expression in the joints and by a reduction in the percentages of invariant NKT (iNKT) cells in the spleen. Immunized CD38 KO mice produce high levels of circulating IgG1 and low of IgG2a anti-col II antibodies in association with reduced percentages of Th1 cells in the draining lymph nodes. Altogether, our results show that CD38 participates in the pathogenesis of CIA controlling the number of iNKT cells and promoting Th1 inflammatory responses.

CD38 protein deficiency induces autoimmune characteristics and its activation enhances IL‐10 production by regulatory B cells

“…CD38 −/ − mice backcrossed into autoimmune diabetes‐prone (NOD)‐developed diabetes faster than the control mice . Additionally, in collagen‐induced arthritis (CIA), autoantibodies are increased in CD38 −/− mice . Finally, a CD38 deficiency accelerated the development of a lupus‐like disease in Cd38 −/− ‐Fas lpr /Fas lpr .…”

Distinct serum proteome profiles associated with collagen‐induced arthritis and complete Freund's adjuvant‐induced inflammation in CD38−/− mice: The discriminative power of protein species or proteoforms

“…Immunized CD38-KO mice produce high levels of circulating IgG 1 and low of IgG 2a anti-Col-II antibodies in association with reduced percentages of T-helper 1 (Th1) cells in the draining lymph nodes. Altogether, the results show that CD38 participates in the pathogenesis of CIA controlling the number of iNKT cells and promoting Th1 inflammatory responses [5].…”

“…In humans, SAA has been successfully validated as part of a novel multibiomarker test to assess RA disease activity termed MBDA [24]. In this sense, another biomarker included in the MBDA test is IL-6 that shows significantly increased gene expression in the joints of Col II-immunized WT mice as compared with CD38-KO mice [5], as well as at protein level in serum samples from the same mice (data not shown).…”

“…For the induction of CIA, [8][9][10][11][12] week-old male mice were immunized as previously described [3,5].…”

“…Therefore, it was of interest to study whether there were differences in serum protein profiles between CIA + and CIA − mice that all were immunized with Col-II/CFA and, therefore, subjected to same inflammatory challenge induced by CFA. On the other hand, the clinical course of arthritis in CD38-KO mice is milder than that in WT mice [5], which opens the question of whether putative differences in serum protein profiles between these mice may reflect a distinct immune response of CD38-KO mice to Col-II/CFA immunization. The goal was to identify proteins that may be posttranslationally modified, or altered in their serum concentration levels in response to Col-II/CFA immunization.…”