What are cytokines and signaling basics
Cytokines are secreted signaling molecules produced by many cell types that bind specific receptors on target cells. They trigger intracellular pathways (e.g. JAK-STAT, NF-κB) to change gene expression and cell function [1]. 

Types include 𝘪𝘯𝘵𝘦𝘳𝘭𝘦𝘶𝘬𝘪𝘯𝘴 (𝘐𝘓-𝘹), 𝘪𝘯𝘵𝘦𝘳𝘧𝘦𝘳𝘰𝘯𝘴 (𝘐𝘍𝘕𝘴), 𝘵𝘶𝘮𝘰𝘳 𝘯𝘦𝘤𝘳𝘰𝘴𝘪𝘴 𝘧𝘢𝘤𝘵𝘰𝘳𝘴 (𝘛𝘕𝘍𝘴), 𝘤𝘰𝘭𝘰𝘯𝘺-𝘴𝘵𝘪𝘮𝘶𝘭𝘢𝘵𝘪𝘯𝘨 𝘧𝘢𝘤𝘵𝘰𝘳𝘴 (𝘊𝘚𝘍𝘴), 𝘤𝘩𝘦𝘮𝘰𝘬𝘪𝘯𝘦𝘴, etc.  

Signaling can be paracrine (cell signals to neighbor), endocrine (via blood to distant cells), or autocrine (cells repsond to their own secreted cytokine).

𝗔𝘂𝘁𝗼𝗰𝗿𝗶𝗻𝗲 𝘀𝗶𝗴𝗻𝗮𝗹𝗶𝗻𝗴 & 𝗲𝘅𝗮𝗺𝗽𝗹𝗲𝘀 𝗶𝗻 𝗶𝗺𝗺𝘂𝗻𝗼𝗹𝗼𝗴𝘆 
Autocrine signaling means a cell produces a cytokine and also expresses its receptor for that cytokine, so it responds to its own signal. 
Example: Activated T cells often produce IL-2, and also express high levels of IL-2 receptor α chain (CD25) — 𝘐𝘓-2 𝘢𝘤𝘵𝘴 𝘪𝘯 𝘢𝘶𝘵𝘰𝘤𝘳𝘪𝘯𝘦 𝘢𝘯𝘥 𝘱𝘢𝘳𝘢𝘤𝘳𝘪𝘯𝘦 𝘧𝘢𝘴𝘩𝘪𝘰𝘯 𝘵𝘰 𝘦𝘹𝘱𝘢𝘯𝘥 𝘛 𝘤𝘦𝘭𝘭𝘴.  

𝗖𝗼𝗻𝗻𝗲𝗰𝘁𝗶𝗼𝗻 𝘁𝗼 𝗖𝗔𝗥-𝗧 𝘁𝗵𝗲𝗿𝗮𝗽𝘆 
CAR-T cells are engineered T cells that recognize cancer antigens via chimeric antigen receptors. 
The massive cytokine surge from CAR-T and bystander immune cells causes 𝗖𝘆𝘁𝗼𝗸𝗶𝗻𝗲 𝗥𝗲𝗹𝗲𝗮𝘀𝗲 𝗦𝘆𝗻𝗱𝗿𝗼𝗺𝗲 (𝗖𝗥𝗦) — systemic inflammation, fever, hypotension, organ dysfunction [3]. 

 German researchers in Regensburg recently reported frequent coagulopathy and hypofibrinogenemia during CRS, underlining the need for close cytokine monitoring. IL-6 blockade (e.g. tocilizumab) is standard for severe CRS [4]. 
Hinrich Abken (Regensburg) and colleagues developed ´cytokine help intensified CAR´ (CHIC) T cells, engineering cytokine signaling loops for improved persistence and reduced toxicity [2]. 

𝗪𝗵𝗮𝘁 𝗳𝗮𝘀𝗰𝗶𝗻𝗮𝘁𝗲𝘀 𝗺𝗲 & 𝘀𝗽𝗲𝗰𝘂𝗹𝗮𝘁𝗶𝘃𝗲 𝗵𝘆𝗽𝗼𝘁𝗵𝗲𝘀𝗶𝘀 
What fascinates me is the fine balance of cytokine signaling: too little → weak immunity; too much → pathology. The same molecule can heal or harm depending on timing, dose, and context.  
Speculative thought: Could future CAR-T be equipped with ´smart cytokine switches´ that sense overload and do shut-down? 

Stay tuned for 𝗗𝗮𝘆 6: What is antigen presentation (MHC-I and MHC-II)? 

𝗥𝗲𝗳𝗲𝗿𝗲𝗻𝗰𝗲𝘀: 
1. https://doi.org/10.1016/j.immuni.2019.03.028 
2. doi: 10.3389/fimmu.2022.1090959 
3. DOI: 10.3322/caac.21702 
4. https://doi.org/10.3324/haematol.2023.284564 

 #100DaysOfImmunology #Cytokines #ImmuneSignaling #CARTCells #CytokineReleaseSyndrome #CRS #Immunotherapy #CancerResearch #ScienceCommunication #TeachingImmunology #MechanisticImmunology #GermanResearch