Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies suggest that the forkhead transcription factor Foxj1 inhibits spontaneous autoimmunity in part by antagonizing NF-kappaB activation. To test this hypothesis, we ectopically expressed Foxj1 in the T cells of lupus-prone MRL/lpr mice by backcrossing a CD2-Foxj1 transgene against the MRL/lpr background. Strikingly, CD2-Foxj1-MRL/lpr animals showed a significant reduction in lymphadenopathy, pathogenic autoantibodies, and end-organ disease-but surprisingly, reversion of autoimmunity was not attributable to modulation of NF-kappaB. Instead, CD2-Foxj1 transgenic mice exhibited a peripheral T cell lymphopenia, associated with an accumulation of mature single-positive thymocytes. Transgenic thymocytes demonstrated unimpaired lymphoid organ entry in adoptive transfer studies but demonstrated impaired thymic exodus in response to CCL19, apparently independent of CCR7, S1P1, and NF-kappaB. These findings confirm the importance of Foxj1 in the regulation of T cell tolerance but furthermore suggest a novel and specific role for Foxj1 in regulating thymic egress.
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PMID:Cutting edge: Foxj1 protects against autoimmunity and inhibits thymocyte egress. 1633 15

Immune recovery after profound lymphopenia is a major challenge in many clinical situations, such as allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recovery depends, in a first step, on hematopoietic lymphoid progenitors production in the bone marrow (BM). In this study, we characterized CD34+Lin-CD10+ lymphoid progenitors in the peripheral blood of allo-HSCT patients. Our data demonstrate a strong recovery of this population 3 months after transplantation. This rebound was abolished in patients who developed acute graft-versus-host disease (aGVHD). A similar recovery profile was found for both CD24+ and CD24- progenitor subpopulations. CD34+lin-CD10+CD24- lymphoid progenitors sorted from allo-HSCT patients preserved their T cell potentiel according to in vitro T-cell differentiation assay and the expression profile of 22 genes involved in T-cell differentiation and homing. CD34+lin-CD10+CD24- cells from patients without aGVHD had reduced CXCR4 gene expression, consistent with an enhanced egress from the BM. CCR7 gene expression was reduced in patients after allo-HSCT, as were its ligands CCL21 and CCL19. This reduction was particularly marked in patients with aGVHD, suggesting a possible impact on thymic homing. Thus, the data presented here identify this population as an important early step in T cell reconstitution in humans and so, an important target when seeking to enhance immune reconstitution.
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PMID:CXCR4-related increase of circulating human lymphoid progenitors after allogeneic hematopoietic stem cell transplantation. 2462 6