PMID- 38396788 OWN - NLM STAT- MEDLINE DCOM- 20240226 LR - 20240313 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 4 DP - 2024 Feb 9 TI - The Differential Effect of a Shortage of Thyroid Hormone Compared with Knockout of Thyroid Hormone Transporters Mct8 and Mct10 on Murine Macrophage Polarization. LID - 10.3390/ijms25042111 [doi] LID - 2111 AB - Innate immune cells, including macrophages, are functionally affected by thyroid hormone (TH). Macrophages can undergo phenotypical alterations, shifting between proinflammatory (M1) and immunomodulatory (M2) profiles. Cellular TH concentrations are, among others, determined by TH transporters. To study the effect of TH and TH transporters on macrophage polarization, specific proinflammatory and immunomodulatory markers were analyzed in bone marrow-derived macrophages (BMDMs) depleted of triiodothyronine (T3) and BMDMs with a knockout (KO) of Mct8 and Mct10 and a double KO (dKO) of Mct10/Mct8. Our findings show that T3 is important for M1 polarization, while a lack of T3 stimulates M2 polarization. Mct8 KO BMDMs are unaffected in their T3 responsiveness, but exhibit slight alterations in M2 polarization, while Mct10 KO BMDMs show reduced T3 responsiveness, but unaltered polarization markers. KO of both the Mct8 and Mct10 transporters decreased T3 availability and, contrary to the T3-depleted BMDMs, showed partially increased M1 markers and unaltered M2 markers. These data suggest a role for TH transporters besides transport of TH in BMDMs. This study highlights the complex role of TH transporters in macrophages and provides a new angle on the interaction between the endocrine and immune systems. FAU - Hoen, Esmee AU - Hoen E AD - Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam Gastroenterology Endocrinology & Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. FAU - Goossens, Franka M AU - Goossens FM AD - Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam Gastroenterology Endocrinology & Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. FAU - Falize, Kim AU - Falize K AD - Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam Gastroenterology Endocrinology & Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. FAU - Mayerl, Steffen AU - Mayerl S AD - Department of Endocrinology, Diabetes & Metabolism, University Duisburg-Essen, 47057 Essen, Germany. FAU - van der Spek, Anne H AU - van der Spek AH AD - Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology & Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. FAU - Boelen, Anita AU - Boelen A AUID- ORCID: 0000-0002-4994-2918 AD - Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam Gastroenterology Endocrinology & Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. LA - eng PT - Journal Article DEP - 20240209 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Monocarboxylic Acid Transporters) RN - 0 (Symporters) RN - 0 (Thyroid Hormones) RN - 06LU7C9H1V (Triiodothyronine) RN - 0 (Slc16a2 protein, mouse) RN - 0 (Slc16a10 protein, mouse) RN - 0 (Amino Acid Transport Systems, Neutral) SB - IM MH - Animals MH - Mice MH - *Macrophages/metabolism MH - Monocarboxylic Acid Transporters/genetics MH - *Symporters/genetics MH - *Thyroid Hormones/metabolism/pharmacology MH - Triiodothyronine/pharmacology MH - Amino Acid Transport Systems, Neutral/genetics/metabolism PMC - PMC10889717 OTO - NOTNLM OT - Mct10 OT - Mct8 OT - T3 OT - bone marrow-derived macrophages OT - innate immune system OT - thyroid hormone OT - thyroid hormone transporters COIS- The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. EDAT- 2024/02/24 11:45 MHDA- 2024/02/26 06:44 PMCR- 2024/02/09 CRDT- 2024/02/24 01:03 PHST- 2023/12/22 00:00 [received] PHST- 2024/01/24 00:00 [revised] PHST- 2024/02/06 00:00 [accepted] PHST- 2024/02/26 06:44 [medline] PHST- 2024/02/24 11:45 [pubmed] PHST- 2024/02/24 01:03 [entrez] PHST- 2024/02/09 00:00 [pmc-release] AID - ijms25042111 [pii] AID - ijms-25-02111 [pii] AID - 10.3390/ijms25042111 [doi] PST - epublish SO - Int J Mol Sci. 2024 Feb 9;25(4):2111. doi: 10.3390/ijms25042111.