PMID- 32296417 OWN - NLM STAT- MEDLINE DCOM- 20210304 LR - 20210304 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - Tissue-Specific Factors Differentially Regulate the Expression of Antigen-Processing Enzymes During Dendritic Cell Ontogeny. PG - 453 LID - 10.3389/fimmu.2020.00453 [doi] LID - 453 AB - Dendritic cells (DCs) form a collection of antigen-presenting cells (APCs) that are distributed throughout the body. Conventional DCs (cDCs), which include the cDC1 and cDC2 subsets, and plasmacytoid DCs (pDCs) constitute the two major ontogenically distinct DC populations. The pDCs complete their differentiation in the bone marrow (BM), whereas the cDC subsets derive from pre-committed BM precursors, the pre-cDC, that seed lymphoid and non-lymphoid tissues where they further differentiate into mature cDC1 and cDC2. Within different tissues, cDCs express distinct phenotype and function. Notably, cDCs in the thymus are exquisitely efficient at processing and presenting antigens in the class II pathway, whereas in the spleen they do so only upon maturation induced by danger signals. To appraise this functional heterogeneity, we examined the regulation of the expression of distinct antigen-processing enzymes during DC ontogeny. We analyzed the expression of cathepsin S (CTSS), cathepsin L (CTSL), and thymus-specific serine protease (TSSP), three major antigen-processing enzymes regulating class II presentation in cDC, by DC BM precursors and immature and mature cDCs from the spleen and thymus. We found that pre-cDCs in the BM express relatively high levels of these different proteases. Then, their expression is modulated in a tissue-specific and subset-specific manner with immature and mature thymic cDCs expressing overall higher levels than immature splenic cDCs. On the other hand, the TSSP expression level is selectively down-regulated in spleen pDCs, whereas CTSS and CTSL are both increased in thymic and splenic pDCs. Hence, tissue-specific factors program the expression levels of these different proteases during DC differentiation, thus conferring tissue-specific function to the different DC subsets. CI - Copyright (c) 2020 Mahiddine, Hassel, Murat, Girard and Guerder. FAU - Mahiddine, Karim AU - Mahiddine K AD - Centre de Physiopathologie de Toulouse Purpan, Institut National de la Sante et de la Recherche Medicale, Centre National de la Recherche Scientifique, Universite Paul Sabatier Toulouse III, Toulouse, France. FAU - Hassel, Chervin AU - Hassel C AD - Centre de Physiopathologie de Toulouse Purpan, Institut National de la Sante et de la Recherche Medicale, Centre National de la Recherche Scientifique, Universite Paul Sabatier Toulouse III, Toulouse, France. FAU - Murat, Claire AU - Murat C AD - Centre de Physiopathologie de Toulouse Purpan, Institut National de la Sante et de la Recherche Medicale, Centre National de la Recherche Scientifique, Universite Paul Sabatier Toulouse III, Toulouse, France. FAU - Girard, Maeva AU - Girard M AD - Centre de Physiopathologie de Toulouse Purpan, Institut National de la Sante et de la Recherche Medicale, Centre National de la Recherche Scientifique, Universite Paul Sabatier Toulouse III, Toulouse, France. FAU - Guerder, Sylvie AU - Guerder S AD - Centre de Physiopathologie de Toulouse Purpan, Institut National de la Sante et de la Recherche Medicale, Centre National de la Recherche Scientifique, Universite Paul Sabatier Toulouse III, Toulouse, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200331 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Cytokines) RN - EC 3.4.- (Cathepsins) RN - EC 3.4.- (Serine Proteases) RN - EC 3.4.22.15 (Cathepsin L) RN - EC 3.4.22.27 (cathepsin S) SB - IM MH - Animals MH - Antigen Presentation MH - Cathepsin L/genetics/*metabolism MH - Cathepsins/genetics/*metabolism MH - Cell Differentiation MH - Cytokines/metabolism MH - Dendritic Cells/*physiology MH - Enzyme Activation MH - Gene Expression Regulation MH - Mice MH - Mice, Inbred C57BL MH - Mice, Inbred NOD MH - Organ Specificity MH - Serine Proteases/genetics/*metabolism MH - Th1 Cells/immunology MH - Th2 Cells/immunology MH - Thymus Gland/*metabolism PMC - PMC7136460 OTO - NOTNLM OT - cathepsin L OT - cathepsin S OT - dendritic cell ontogeny OT - splenic dendritic cell OT - thymic dendritic cell OT - thymus-specific serine protease EDAT- 2020/04/17 06:00 MHDA- 2021/03/05 06:00 PMCR- 2020/01/01 CRDT- 2020/04/17 06:00 PHST- 2019/11/02 00:00 [received] PHST- 2020/02/27 00:00 [accepted] PHST- 2020/04/17 06:00 [entrez] PHST- 2020/04/17 06:00 [pubmed] PHST- 2021/03/05 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.00453 [doi] PST - epublish SO - Front Immunol. 2020 Mar 31;11:453. doi: 10.3389/fimmu.2020.00453. eCollection 2020.